Robert L Danner

National Institutes of Health, Maryland, United States

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Publications (181)1084.12 Total impact

  • Sameer S Kadri, Robert L Danner
    Annals of internal medicine 11/2014; 161(10):JC12. · 13.98 Impact Factor
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    ABSTRACT: Background: Necrotizing fasciitis (NF) is a rare, rapidly progressing, severe subtype of necrotizing skin and soft-tissue infection (NSSTI) that in 30-50% of cases presents with toxic shock syndrome (TSS). Intravenous immune globulin (IVIG) has been recommended for TSS, but level-1 evidence is lacking. However, IVIG administration might be used to identify likely cases of NF-related TSS among patients with NSSTIs that otherwise require vasopressor support for shock. Methods: An administrative database of 110 academic medical centers containing individual charges related to drugs and days of therapy was queried for adult cases with an International Classification of Diseases-Version 9 (ICD-9) diagnostic code for NF, Gas or Fournier's Gangrene and at least 1 ICD-9 procedure code for surgical debridement between October 2010 and February 2014. Cases were dichotomized based on use of IVIG. Analyses were restricted to cases with vasopressor dependent shock in the major and extreme categories of the 3M All Patients Refined Diagnoses Related Group Severity of Illness (SOI) scale. The primary outcome was in-hospital mortality and secondary outcomes were mean duration on vasopressors and mean direct hospital costs. Results: Of 4221 adults with NSSTIs, vasopressor dependent shock and undergoing surgical debridement, only 147 (3.5%) received IVIG. Among those in the major and extreme categories of SOI, in-hospital mortality was higher in the IVIG group at 19.9% (28/141) than in the non-IVIG group at 14.8% (558/3766) but the difference was not significant (p=0.10). IVIG patients remained on vasopressors longer (10.4 ± 9.5 days vs. 5.5 ± 7.5 days; p< 0.0001). Direct healthcare costs were twice as high in the IVIG group at $119,698 ± $118,232/case (p< 0.0001). Conclusion: Use of IVIG in cases of NSSTIs with vasopressor dependent shock is rare. This likely reflects both the small proportion of these cases that meet criteria for NF-related TSS, as well as inconsistent use of this still controversial intervention. Adult cases of NSSTI with vasopressor dependent shock that received IVIG stayed in shock longer and bore higher healthcare costs. IVIG administration identifies a very sick subpopulation of NSSTIs associated with shock.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: The clinical significance and even existence of critical illness-related corticosteroid insufficiency is controversial. Here, hypothalamic-pituitary-adrenal (HPA) function was characterized in severe canine Staphylococcus aureus pneumonia. Animals received antibiotics and titrated life supportive measures. Treatment with dexamethasone, a glucocorticoid, but not desoxycorticosterone, a mineralocorticoid, improves outcome in this model. Total and free cortisol, adrenocorticotropic hormone (ACTH) and aldosterone levels, as well as responses to exogenous ACTH were measured serially. At 10h after the onset of infection, the acute HPA axis stress-response, as measured by cortisol levels, exceeded that seen with high-dose ACTH stimulation, but was not predictive of outcome. In contrast to cortisol, aldosterone was largely autonomous from HPA axis control, elevated longer, and more closely associated with survival in early septic shock. Importantly, dexamethasone suppressed cortisol and ACTH levels and restored ACTH responsiveness in survivors. Differing strikingly non-survivors, sepsis-induced hypercortisolemia and high ACTH levels as well as ACTH hypo-responsiveness were not influenced by dexamethasone. During septic shock, only serial measurements and provocative testing over a well-defined timeline was able to demonstrate a strong relationship between HPA axis function and prognosis. HPA axis unresponsiveness and high aldosterone levels identify a septic shock subpopulation with poor outcomes that may have the greatest potential to benefit from new therapies.
    American journal of physiology. Endocrinology and metabolism. 10/2014;
  • Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 09/2014;
  • Blood 08/2014; 124(7):1198-9. · 9.78 Impact Factor
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    ABSTRACT: Accurately detecting circulating endothelial cells (CECs) is important since their enumeration has been proposed as a biomarker to measure injury to the vascular endothelium. However, there is no single methodology for determining CECs in blood, making comparison across studies difficult. Many methods for detecting CECs rely on characteristic cell surface markers and cell viability indicators, but lack secondary validation. Here, a CEC population in healthy adult human subjects was identified by flow cytometry as CD45-, CD34dim that is comparable to a previously described CD45-, CD31bright population. In addition, nuclear staining with 7-aminoactinomycin D (7-AAD) was employed as a standard technique to exclude dead cells. Unexpectedly, the CD45-, CD34dim, 7-AAD- CECs lacked surface detectable CD146, a commonly used marker of CECs. Furthermore, light microscopy revealed this cell population to be composed primarily of large cells without a clearly defined nucleus. Nevertheless, immunostains still demonstrated the presence of the lectin Ulex europaeus and von Willebrand factor. Ultramicro analytical immunochemistry assays for the endothelial cell proteins CD31, CD34, CD62E, CD105, CD141, CD144 and vWF indicated these cells possess an endothelial phenotype. However, only a small amount of RNA, which was mostly degraded, could be isolated from these cells. Thus the majority of CECs in healthy individuals as defined by CD45-, CD34dim, and 7-AAD- have shed their CD146 surface marker and are senescent cells without an identifiable nucleus and lacking RNA of sufficient quantity and quality for transcriptomal analysis. This study highlights the importance of secondary validation of CEC identification.
    Thrombosis and haemostasis. 07/2014; 112(4).
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    ABSTRACT: Lung nodules are common diagnostic challenges in hematopoietic stem cell transplantation and solid organ transplantation. Pseudomonas aeruginosa is a known cause of lung abscess in these patients, but its ability to persist for months in a quiescent lung nodule and later cause recurrent infection is not well known or documented. A patient with a history of acute pre-B-cell lymphoblastic leukemia had enlargement and cavitation of a small right upper lobe pulmonary nodule 10 months after allogeneic hematopoietic stem cell transplantation. The nodule was the remnant of a presumed P. aeruginosa septic embolus that occurred 2.5 months after transplantation. With antibiotic treatment, the nodule had shrunk in size to <1 cm and remained stable. Transthoracic needle aspiration grew P. aeruginosa indistinguishable by molecular typing from isolates obtained 7.5 months earlier from blood and bronchoalveolar lavage fluid. Sub-centimeter pulmonary nodules attributable to previously treated P. aeruginosa may harbor viable organisms and lead to recrudescent infection.
    Transplant Infectious Disease 06/2014; · 1.98 Impact Factor
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    ABSTRACT: Bacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB) challenge was investigated in six tissues. The earliest responses and largest number of affected genes occurred in peripheral blood mononuclear cells (PBMC), spleen, and lung tissues with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney, and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Nine of the 85 genes were subsequently confirmed by RT-PCR in every tissue/organ at 24 h. These 85 transcripts, up-regulated in all tissues, annotated to the interferon (IFN)/antiviral-response and included genes belonging to the DNA/RNA sensing system, DNA damage repair, the immunoproteasome, and the ER/metabolic stress-response and apoptosis pathways. Overall, this shared program was identified as a type I and II interferon (IFN)-response and the promoters of these genes were highly enriched for IFN regulatory matrices. Several genes whose secreted products induce the IFN pathway were up-regulated at early time points in PBMCs, spleen, and/or lung. Furthermore, IFN regulatory factors including Irf1, Irf7 and Irf8, and Zbp1, a DNA sensor/transcription factor that can directly elicit an IFN innate immune response, participated in this host-wide SEB signature. Global gene-expression changes across multiple organs implicated a host-wide IFN-response in SEB-induced death. Therapies aimed at IFN-associated innate immunity may improve outcome in toxic shock syndromes.
    PLoS ONE 01/2014; 9(2):e88756. · 3.53 Impact Factor
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    ABSTRACT: Dendritic cells (DCs) comprise distinct populations with specialized immune-regulatory functions. However, the environmental factors that determine the differentiation of these subsets remain poorly defined. Here, we report that retinoic acid (RA), a vitamin A derivative, controls the homeostasis of pre-DC (precursor of DC)-derived splenic CD11b(+)CD8α(-)Esam(high) DCs and the developmentally related CD11b(+)CD103(+) subset within the gut. Whereas mice deprived of RA signaling significantly lost both of these populations, neither pre-DC-derived CD11b(-)CD8α(+) and CD11b(-)CD103(+) nor monocyte-derived CD11b(+)CD8α(-)Esam(low) or CD11b(+)CD103(-) DC populations were deficient. In fate-tracking experiments, transfer of pre-DCs into RA-supplemented hosts resulted in near complete conversion of these cells into the CD11b(+)CD8α(-) subset, whereas transfer into vitamin A-deficient (VAD) hosts caused diversion to the CD11b(-)CD8α(+) lineage. As vitamin A is an essential nutrient, we evaluated retinoid levels in mice and humans after radiation-induced mucosal injury and found this conditioning led to an acute VAD state. Consequently, radiation led to a selective loss of both RA-dependent DC subsets and impaired class II-restricted auto and antitumor immunity that could be rescued by supplemental RA. These findings establish a critical role for RA in regulating the homeostasis of pre-DC-derived DC subsets and have implications for the management of patients with immune deficiencies resulting from malnutrition and irradiation.
    Journal of Experimental Medicine 09/2013; · 13.21 Impact Factor
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    ABSTRACT: We studied the changes in expression of microRNAs and mRNA in normal human bronchial epithelial cells as they differentiate from an undifferentiated monolayer to a differentiated pseudostratified epithelium after 28 days of air/liquid interface (ALI) culture. After 28 days in ALI, the epithelial cells differentially expressed basal, ciliated and goblet cell markers. Using Affymetrix microarrays, 20 human miRNAs were found to be up-regulated while 35 miRNAs were found to be down-regulated in differentiated compared to undifferentiated cells. An analysis of changes in global mRNA expression revealed that 1201 probesets demonstrated an 8-fold change or greater at day 28 of ALI culture. Of these, 816 were up-regulated and 385 were down-regulated. With differentiation, miR-449a increased [fold change (FC), 38.15], and was related to changes in mRNA for Cell Division Cycle 25 Homologue A, CDC25A, (FC, 0.11). MiR -455 decreased (FC, 0.12) and was related to changes in mRNA for the epithelial cell marker, MUC1, (FC, 136). Transfection with antimiR-449 or miR-455-3p resulted in changes in target protein expression (CDC25A and MUC1, respectively) while transfection with reporter genes with 3'UTRs of these targets confirmed control of expression through that structure. Therefore, changes in specific miRNAs during human airway epithelial cell differentiation control gene and protein expression important for differentiation.
    American Journal of Respiratory Cell and Molecular Biology 04/2013; · 4.15 Impact Factor
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    ABSTRACT: BACKGROUND: Pulmonary arterial hypertension is a rare disorder associated with poor survival. Endothelial dysfunction plays a central role in the pathogenesis and progression of pulmonary arterial hypertension. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic and disease-associated pulmonary arterial hypertension. Therapy targeting pulmonary vascular inflammation to interrupt cycles of injury and repair and thereby delay or prevent right ventricular failure and death has not been tested. Spironolactone, a mineralocorticoid and androgen receptor antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with pulmonary arterial hypertension and symptoms of right heart failure includes use of mineralocorticoid receptor antagonists for their diuretic and natriuretic effects. We hypothesize that initiating spironolactone therapy at an earlier stage of disease in patients with pulmonary arterial hypertension could provide additional benefits through anti-inflammatory effects and improvements in pulmonary vascular function. METHODS: Seventy patients with pulmonary arterial hypertension without clinical evidence of right ventricular failure will be enrolled in a randomized, double-blinded, placebo-controlled trial to investigate the effect of early treatment with spironolactone on exercise capacity, clinical worsening and vascular inflammation in vivo. Our primary endpoint is change in placebo-corrected 6-minute walk distance at 24 weeks and the incidence of clinical worsening in the spironolactone group compared to placebo. At a two-sided alpha level of 0.05, we will have at least 84% power to detect an effect size (group mean difference divided by standard deviation) of 0.9 for the difference in the change of 6-minute walk distance from baseline between the two groups. Secondary endpoints include the effect of spironolactone on the change in placebo-corrected maximal oxygen consumption; plasma markers of vascular inflammation and peripheral blood mononuclear cell gene expression profiles; sympathetic nervous system activation, renin-angiotensin-aldosterone system activation and sex hormone metabolism; and right ventricular structure and function using echocardiography and novel high-resolution magnetic resonance imaging-based techniques. Safety and tolerability of spironolactone will be assessed with periodic monitoring for hyperkalemia and renal insufficiency as well as the incidence of drug discontinuation for untoward effects.Trial registration: ClinicalTrials.gov: NCT01712620.
    Trials 04/2013; 14(1):91. · 2.21 Impact Factor
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    ABSTRACT: There is a paucity of pharmacokinetic studies describing weight-based dosing of intravenous voriconazole in obese patients. In this case report, we describe the pharmacokinetics of intravenous voriconazole in an obese CYP2C19 homozygous poor metabolizer and review previously reported data regarding the use of intravenous voriconazole in obese patients. A 17-year-old obese Hispanic male patient (body mass index 35 kg/m ) received intravenous voriconazole for the treatment of suspected aspergillosis. After 2.5 days of voriconazole 4 mg/kg intravenously every 12 hours based on adjusted body weight, the voriconazole area under the serum concentration-time curve over the course of a single (12-hr) dosing interval and trough concentration were 86,100 ng · hr/ml and 6.2 µg/ml, respectively. Six days later, the voriconazole dosage was decreased. A trough concentration measured just before the dosage reduction (after 8.5 days of voriconazole 4 mg/kg intravenously every 12 hours based on adjusted body weight) remained elevated at 5.8 µg/ml. Genotyping revealed a CYP2C19 homozygous poor metabolizer (CYP2C19*2/*2). Voriconazole was subsequently discontinued due to QTc prolongation. These data and those from two recent publications suggest that voriconazole does not distribute extensively into human adipose tissue and that obese patients should be dosed on an adjusted body weight basis. If an obese patient dosed on total body weight is also a CYP2C19 poor metabolizer, serum voriconazole concentrations will be further elevated, potentially leading to drug-induced toxicity.
    Pharmacotherapy 03/2013; 33(3):e19-22. · 2.31 Impact Factor
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    ABSTRACT: Purpose: Human immunodeficiency virus (HIV)-related fatigue (HRF) is multicausal and potentially related to mitochondrial dysfunction caused by antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs). Methodology: The authors compared gene expression profiles of CD14+ cells of low versus high fatigued, NRTI-treated HIV patients to healthy controls (n = 5/group). The authors identified 32 genes predictive of low versus high fatigue and 33 genes predictive of healthy versus HIV infection. The authors constructed genetic networks to further elucidate the possible biological pathways in which these genes are involved. Relevance for nursing practice: Genes including the actin cytoskeletal regulatory proteins Prokineticin 2 and Cofilin 2 along with mitochondrial inner membrane proteins are involved in multiple pathways and were predictors of fatigue status. Previously identified inflammatory and signaling genes were predictive of HIV status, clearly confirming our results and suggesting a possible further connection between mitochondrial function and HIV. Isolated CD14+ cells are easily accessible cells that could be used for further study of the connection between fatigue and mitochondrial function of HIV patients. Implication for Practice: The findings from this pilot study take us one step closer to identifying biomarker targets for fatigue status and mitochondrial dysfunction. Specific biomarkers will be pertinent to the development of methodologies to diagnosis, monitor, and treat fatigue and mitochondrial dysfunction.
    Biological Research for Nursing 01/2013; · 1.85 Impact Factor
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    ABSTRACT: PURPOSE: The effects of stress-dose corticosteroid therapy were studied in a canine staphylococcal pneumonia model of septic shock. METHODS: Immediately following intrabronchial bacterial challenge, purpose-bred beagles were treated with stress doses of desoxycorticosterone (DOC), a mineralocorticoid agonist, and dexamethasone (DEX), a glucocorticoid agonist, or with placebo for 96 h. Oxacillin (30 mg/kg every 8 h) was started 4 h after infection onset. Bacterial dose was titrated to achieve 80-90 % lethality (n = 20) using an adaptive design; additional animals (n = 18) were investigated using the highest bacterial dose. RESULTS: Initial analysis of all animals (n = 38) demonstrated that the effects of DOC + DEX were significantly altered by bacterial dose (p = 0.04). The treatment effects of DOC + DEX were different in animals administered high or relatively lower bacterial doses in terms of survival (p = 0.05), shock reversal (p = 0.02), interleukin-6 levels (p = 0.02), and temperature (p = 0.01). DOC + DEX significantly improved the above parameters (p ≤ 0.03 for all) and lung injury scores (p = 0.02) after high-dose bacterial challenges, but not after lower challenges (p = not significant for all). Oxacillin trough levels were below the minimum inhibitory concentration of the infecting organism, and DOC + DEX increased the frequency of persistent staphylococcal bacteremia (odds ratio 3.09; 95 % confidence interval 1.05-9.11; p = 0.04). CONCLUSIONS: Stress-dose corticosteroids were only beneficial in cases of sepsis with high risk for death and even short courses may interfere with host mechanisms of bacterial clearance.
    European Journal of Intensive Care Medicine 10/2012; · 5.17 Impact Factor
  • Jason M Elinoff, Robert L Danner
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    ABSTRACT: QUESTION In adults with severe sepsis, what are the relative efficacy and safety of hydroxyethyl starch (HES) 130/0.42 and Ringer's acetate for fluid resuscitation? METHODS DESIGN Randomized controlled trial (RCT) (Scandinavian Starch for Severe Sepsis/Septic Shock [6S] trial). ClinicalTrials.gov NCT00962156. ALLOCATION Concealed.* BLINDING Blinded* (patients, clinicians, research staff, safety committee, manuscript writers, and statisticians). FOLLOW-UP PERIOD 90 days. SETTING 26 intensive care units (ICUs) in Denmark, Norway, Finland, and Iceland. PATIENTS 804 ICU patients ≥ 18 years of age (median age 67 y, 61% men) who had severe sepsis (defined focus of infection and ≥ 2 systemic inflammatory response syndrome criteria) in the previous 24 hours and needed fluid resuscitation. Exclusion criteria included > 1000 mL of synthetic colloid in the previous 24 hours; renal replacement therapy; acute burn injury to > 10% of body surface; severe hyperkalemia; or liver or kidney transplantation or intracranial bleeding during current hospitalization. INTERVENTION 6% HES 130/0.42 in Ringer's acetate (Tetraspan 6%, B Braun) (n = 400) or Ringer's acetate (Sterofundin ISO, B Braun) (n = 400) to a maximum daily dose of 33 mL/kg ideal body weight administered intravenously for ≤ 90 days. OUTCOMES Primary outcome was a composite of death or dependence on dialysis (any renal replacement therapy from 86 to 94 d after randomization) at 90 days. Secondary outcomes included components of the composite endpoint, any renal replacement therapy, and severe bleeding (≥ 3 units of packed red cells within 24 h). PATIENT FOLLOW-UP 99% (modified intention-to-treat analysis). MAIN RESULTS The main results are in the Table. CONCLUSION In patients with severe sepsis needing fluid resuscitation, hydroxyethyl starch 130/0.42 increased death at 90 days and need for renal replacement therapy compared with Ringer's acetate.Hydroxyethyl starch (HES) 130/0.42 vs Ringer's acetate for fluid resuscitation in patients with severe sepsis†OutcomesEvent ratesAt 90 dHESRinger's acetateRRI (95% CI)NNH (CI)Death or dependence on dialysis‡51%43%17% (1 to 36)14 (7 to 232)Death51%43%17% (1 to 36)14 (7 to 233)Any renal replacement therapy22%16%35% (1 to 80)18 (8 to 616)Severe bleeding§10%6%52% (-6 to 148)NS†NS = not significant; other abbreviations defined in Glossary. RRI, NNH, and CI calculated from control event rates and relative risks in article.‡1 patient in each group was dependent on dialysis at 90 days.§≥ 3 units of packed red cells within 24 h.
    Annals of internal medicine 10/2012; 157(8):JC4-6. · 13.98 Impact Factor
  • Clinical Infectious Diseases 09/2012; · 9.37 Impact Factor
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
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    ABSTRACT: Although human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) affect mitochondrial DNA (mtDNA) content and function, comprehensive evaluations of their effects on mitochondria in muscle, adipose tissue, and blood cells are limited. Mitochondrial DNA quantification, mitochondrial genome sequencing, and gene expression analysis were performed on muscle, adipose tissue, and peripheral blood mononuclear cell (PBMC) samples from untreated HIV-positive patients, HIV-positive patients receiving nucleoside reverse transcriptase inhibitor (NRTI)-based ART, and HIV-negative controls. The adipose tissue mtDNA/nuclear DNA (nDNA) ratio was increased in untreated HIV-infected patients (ratio, 353) and decreased in those receiving ART (ratio, 162) compared with controls (ratio, 255; P < .05 for both comparisons); the difference between the 2 HIV-infected groups was also significant (P = .002). In HIV-infected participants, mtDNA/nDNA in adipose tissue correlated with the level of activation (CD38+ /HLA-DR+) for CD4+ and CD8+ lymphocytes. No significant differences in mtDNA content were noted in muscle or PMBCs among groups. Exploratory DNA microarray analysis identified differential gene expression between patient groups, including a subset of adipose tissue genes. HIV infection and ART have opposing effects on mtDNA content in adipose tissue; immune activation may mediate the effects of HIV, whereas NRTIs likely mediate the effects of ART.
    The Journal of Infectious Diseases 04/2012; 205(12):1778-87. · 5.85 Impact Factor
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    ABSTRACT: On the basis of noninferiority trials, tigecycline received Food and Drug Administration (FDA) approval in 2005. In 2010, the FDA warned in a safety communication that tigecycline was associated with an increased risk of death. PubMed, EMBASE, Scopus, and ClinicalTrials.gov were searched using the terms "tigecycline" and "randomized controlled trial (RCT)" through April 2011. Excess deaths and noncure rates for both approved and nonapproved indications were examined using meta-analysis. Ten published and 3 unpublished studies met inclusion criteria (N = 7434). No significant heterogeneity was seen for mortality (I(2 )= 0%; P = .99) or noncure rates (I(2 )= 25%; P = .19). Across randomized controlled trials, tigecycline was associated with increased mortality (risk difference [RD], 0.7%; 95% confidence interval [CI], 0.1%-1.2%; P = .01) and noncure rates (RD, 2.9%; 95% CI, 0.6%-5.2%; P = .01). Effects were not isolated to type of infection or comparator antibiotic regimen, and the impact on survival remained significant when limited to trials of approved indications (I(2 )= 0%; RD, 0.6%; P = .04). A pooled analysis of the 5 trials completed by early 2005 before tigecycline was approved would have demonstrated a similar harmful effect of tigecycline on survival (I(2 )= 0%; RD, 0.7%; P = .06). Pooling noninferiority studies to examine survival may help ensure the safety and efficacy of new antibiotics. The association of tigecycline with excess deaths and noncure includes indications for which it is approved and marketed. Tigecycline cannot be relied on in serious infections.
    Clinical Infectious Diseases 03/2012; 54(12):1699-709. · 9.37 Impact Factor
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    ABSTRACT: Th17 cells have been described as short lived, but this view is at odds with their capacity to trigger protracted damage to normal and transformed tissues. We report that Th17 cells, despite displaying low expression of CD27 and other phenotypic markers of terminal differentiation, efficiently eradicated tumors and caused autoimmunity, were long lived, and maintained a core molecular signature resembling early memory CD8(+) cells with stem cell-like properties. In addition, we found that Th17 cells had high expression of Tcf7, a direct target of the Wnt and β-catenin signaling axis, and accumulated β-catenin, a feature observed in stem cells. In vivo, Th17 cells gave rise to Th1-like effector cell progeny and also self-renewed and persisted as IL-17A-secreting cells. Multipotency was required for Th17 cell-mediated tumor eradication because effector cells deficient in IFN-γ or IL-17A had impaired activity. Thus, Th17 cells are not always short lived and are a less-differentiated subset capable of superior persistence and functionality.
    Immunity 12/2011; 35(6):972-85. · 19.80 Impact Factor

Publication Stats

5k Citations
1,084.12 Total Impact Points

Institutions

  • 1988–2014
    • National Institutes of Health
      • • Center for Clinical Research
      • • Pharmacy Department
      • • Critical Care Medicine Department
      Maryland, United States
  • 2013
    • National Institute of Allergy and Infectious Disease
      Maryland, United States
  • 2009–2013
    • National Cancer Institute (USA)
      Maryland, United States
    • The Children's Hospital of Philadelphia
      Philadelphia, Pennsylvania, United States
  • 2001–2013
    • University of Washington Seattle
      • • Department of Biobehavioral Nursing and Health Systems
      • • Department of Surgery
      Seattle, WA, United States
  • 2012
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States
  • 2011
    • University of Texas Health Science Center at San Antonio
      San Antonio, Texas, United States
    • National Heart, Lung, and Blood Institute
      Maryland, United States
    • University of Pennsylvania
      • Division of Cardiovascular Medicine
      Philadelphia, PA, United States
  • 2008–2009
    • Washington University in St. Louis
      • Department of Surgery
      San Luis, Missouri, United States
  • 1989–2008
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Parasitic Diseases (LPD)
      Maryland, United States
    • National Eye Institute
      Maryland, United States
  • 2007
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 2006
    • University of Nebraska at Omaha
      • Department of Internal Medicine
      Omaha, NE, United States
  • 2004
    • Johns Hopkins University
      • Division of Pulmonary and Critical Care Medicine
      Baltimore, MD, United States
  • 1997
    • Tel Aviv University
      Tell Afif, Tel Aviv, Israel
  • 1993
    • Georgetown University
      • Division of Pulmonary and Critical Care Medicine
      Washington, D. C., DC, United States
    • Children's National Medical Center
      Washington, Washington, D.C., United States