Chris Reilly

Chris Reilly
Edward Via College of Osteopathic Medicine | VCOM

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138
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Publications

Publications (138)
Article
Full-text available
Double negative T (DNT) cells are a unique subset of CD3 + TCRαβ + T lymphocytes that lack CD4, CD8, or NK1.1 expression and constitute 3–5% of the total T cell population in C57BL/6 mice. They have increasingly gained recognition for their novel roles in the immune system, especially under autoimmune conditions. Conventional machine learning appro...
Article
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Systemic lupus erythematosus is an autoimmune disease characterized by excessive inflammation and production of pathogenic Abs. Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase. It has been reported that selective HDAC6 inhibition decreases inflammation in lupus mouse models. In this study, sex- and age-matched wild-type (WT) and HD...
Article
The CX3CR1 chemokine receptor initiates intracellular signaling cascades responsible for cellular activity, proliferation, and survival. CX3CR1 loss-of-function leads to exacerbation of chronic kidney disease in patients. Renal disease is a severe complication that often occurs in patients with systemic lupus erythematosus (SLE). We had previously...
Article
Full-text available
Aryl hydrocarbon receptor (AhR) responds to endogenous and exogenous ligands as a cytosolic receptor, transcription factor, and E3 ubiquitin ligase. Several studies support an anti-inflammatory effect of AhR activation. However, exposure to the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during early stages of development results in an a...
Article
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Introduction Leaky gut has been linked to autoimmune disorders including lupus. We previously reported upregulation of anti-flagellin antibodies in the blood of lupus patients and lupus-prone mice, which led to our hypothesis that a leaky gut drives lupus through bacterial flagellin-mediated activation of toll-like receptor 5 (TLR5). Methods We cr...
Article
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Systemic lupus erythematosus (SLE) is a systemic chronic disease initiated by an abnormal immune response to self and can affect multiple organs. SLE is characterized by the production of autoantibodies and the deposition of immune complexes. In regard to the clinical observations assessed by rheumatologists, several chemokines and cytokines also c...
Article
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We previously demonstrated that the upregulation of microRNAs (miRNAs) at the genomic imprinted Dlk1-Dio3 locus in murine lupus is correlated with global DNA hypomethylation. We now report that the Dlk1-Dio3 genomic region in CD4+ T cells of MRL/lpr mice is hypomethylated, linking it to increased Dlk1-Dio3 miRNA expression. We evaluated the gene ex...
Article
A leaky gut has been linked to numerous autoimmune disorders, including systemic lupus erythematosus (SLE). We had previously reported significant upregulation of anti-flagellin antibodies in the blood of SLE patients and lupus-prone MRL/lpr mice, which led to our hypothesis that a leaky gut drove SLE through bacterial flagellin-mediated activation...
Article
Full-text available
Objective Patients with systemic lupus erythematosus (SLE) often develop multi-organ damages including heart and kidney complications. We sought to better define the underlying mechanisms with a focus on the chemokine receptor CX3CR1. Methods We generated Cx3cr1-deficient MRL/lpr lupus-prone mice through backcrossing. We then employed heterozygous...
Article
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Vitamin A (VA) deficiency (VAD) is observed in both humans and mice with lupus nephritis. However, whether VAD is a driving factor for accelerated progression of lupus nephritis is unclear. In this study, we investigated the effect of VAD on the progression of lupus nephritis in a lupus-prone mouse model, MRL/lpr. We initiated VAD either during ges...
Conference Paper
Full-text available
Commensal bacteria and the immune system have a close and strong relationship that maintains a balance to control inflammation. Alterations of the microbiota, known as dysbiosis, can direct reactivity to self-antigens not only in the intestinal mucosa but also at the systemic level. Our laboratory previously reported gut dysbiosis, particularly low...
Conference Paper
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Our recent study has demonstrated induction of regulatory B cells (Bregs) by bacterial DNA in MRL/lpr mice leading to attenuation of SLE. This suggests a regulatory role for the gut bacteria in SLE development. However, the mechanism by which bacterial DNA induces Breg cell differentiation remains to be elucidated. Bacterial DNA contains unmethylat...
Article
Full-text available
Commensal bacteria and the immune system have a close and strong relationship that maintains a balance to control inflammation. Alterations of the microbiota, known as dysbiosis, can direct reactivity to self-antigens not only in the intestinal mucosa but also at the systemic level. Our laboratory previously reported gut dysbiosis, particularly low...
Article
Full-text available
Dysregulated miRNAs have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Our previous study reported a substantial increase in three miRNAs located at the miR-183-96-182 cluster (miR-183C) in several autoimmune lupus-prone mice, including MRL/lpr and C57BL/6-lpr (B6/lpr). This study reports that in vitro inhibition of miR...
Article
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Previous studies have reported that deletion of the transcription factor, early growth response protein 2 (EGR2), in normal C57BL/6 (B6) resulted in the development of lupus-like autoimmune disease. However, increased EGR2 expression has been noted in human and murine lupus, which challenges the notion of the autoimmune suppressive role of EGR2 in...
Article
Transcription factor early growth response protein 2 (EGR2) prevents the development of lupus-like autoimmune disease in C57BL/6 (B6) mice by negatively regulating T cell activation, inflammatory cytokine IFNγ and IL-17 production and by suppressing humoral responses. However, increased EGR2 expression has been observed in lupus and also other auto...
Article
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. The cause of SLE is not only genetic; in fact, environmental factors may play a more important role in disease development. The MRL/lpr mouse model lupus-like symptoms due to multiple SLE susceptible loci in the MRL background, and offers an accelerated model compared to the M...
Article
Full-text available
MRL/lpr mice have been extensively used as a murine model of lupus. Disease progression in MRL/lpr mice can differ among animal facilities, suggesting a role for environmental factors. We noted a phenotypic drift of our in-house colony, which was the progeny of mice obtained from The Jackson Laboratory (JAX; stocking number 000485), that involved a...
Article
Early growth response protein 2 (EGR2) is a zinc-finger transcription factor that belongs to the early growth response (Egr) gene family. Recent studies have shown that EGR2 is required to induce T cell anergy, and it plays an important role in T cell immunity and autoimmunity. Conditional depletion of EGR2 in T lymphocytes in C57BL/6 (B6) mice (EG...
Article
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with no known cure. Gut microbiota and the immune system have a close relationship that controls inflammation. Alterations in the gut microbiota, known as dysbiosis, can trigger SLE in both human and mouse. We previously published differences between the gut microbiota in lupus...
Article
The miR-183-96-182 (miR-183C) is a highly conserved miRNA cluster among species. Our previous work found a significant upregulation of miR-183C in the splenic cells of three different murine models of systemic lupus erythematosus (SLE). Current studies revealed that miR-183C miRNAs are critically involved in immunity and autoimmunity. In this study...
Article
Vitamin A deficiency (VAD) is observed in both human and mice with lupus nephritis (LN). However, whether VAD is a driving factor for LN progression is unclear. Here, we investigated the effect of VAD on the progression of LN in a lupus-prone mouse model, MRL/lpr. In these mice, while LN is not apparent before 8 weeks of age, the inflammation of ly...
Article
Full-text available
Significance Infants are born without an established gut microbiota, which develops rapidly after birth and is shaped by the maternal microbiota. However, how the maternal microbiota, through shaping the neonatal microbiota, would affect the establishment of a strong immune system in neonates remains unclear. Here, we show mechanistically how the m...
Article
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Autoimmune diseases, such as systemic lupus erythematosus, are characterized by excessive inflammation in response to self-antigens. Loss of appropriate immunoregulatory mechanisms contribute to disease exacerbation. We previously showed the suppressive effect of vancomycin treatment during the “active-disease” stage of lupus. In this study, we sou...
Article
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Background: Recent studies have shown that early growth response 2 (EGR2) is highly induced in activated T cells and regulates T cell functions. In normal C57BL/6 (B6) mice, deletion of EGR2 in lymphocytes results in the development of lupus-like systemic autoimmune disease, which implies indirectly an autoimmune protective role of EGR2. Conversel...
Article
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We previously showed that all-trans-retinoic acid (tRA), an active metabolite of vitamin A, exacerbated pre-existing autoimmunity in lupus; however, its effects before the development of autoimmunity are unknown. Here, using a pristane-induced model, we show that tRA exerts differential effects when given at the initiation vs. continuation phase of...
Article
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Autoantibody production by plasma cells (PCs) plays a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). The molecular pathways by which B cells become pathogenic PC secreting autoantibodies in SLE are incompletely characterized. Histone deactylase 6 (HDAC6) is a unique cytoplasmic HDAC that modifies the interaction of a number...
Article
Full-text available
Background: Dysbiosis of gut microbiota exists in the pathogenesis of many autoimmune diseases, including systemic lupus erythematosus (lupus). Lupus patients who experienced pregnancy usually had more severe disease flares post-delivery. However, the possible role of gut microbiota in the link between pregnancy and exacerbation of lupus remains t...
Article
Dysbiosis of gut microbiota exists in the pathogenesis of many autoimmune diseases, including lupus. Currently, women with lupus are recommended to avoid pregnancy, as lupus patients who experienced pregnancy usually had more severe disease flares. However, the possible role of gut microbiota in the link between pregnancy and exacerbation of lupus...
Conference Paper
Background Autoantibody production by plasma cells (PC) play a pivotal role in pathogenesis in of lupus nephritis (LN). The mechanism(s) of how B cells become pathogenic PC secreting autoantibody in SLE is incompletely characterized. In the current study, sought to determine if selective histone deacetylase (HDAC)6 inhibition would abrogate abnorma...
Article
Full-text available
Gut microbiota dysbiosis has been observed in a number of autoimmune diseases. However, the role of gut microbiota in systemic lupus erythematosus (SLE), a prototypical autoimmune disease characterized by persistent inflammation in multiple organs of the body, remains elusive. Here we report the dynamics of gut microbiota in a murine lupus model, N...
Article
Full-text available
Gut microbiota and the immune system interact to maintain tissue homeostasis, but whether this interaction is involved in the pathogenesis of systemic lupus erythematosus (SLE) is unclear. Here we report that oral antibiotics given during active disease removed harmful bacteria from the gut microbiota and attenuated SLE-like disease in lupus-prone...
Article
Full-text available
We have previously demonstrated that HDAC6 expression is increased in animal models of systemic lupus erythematosus (SLE) and that inhibition of HDAC6 decreased disease. In our current studies, we tested if an orally active selective HDAC6 inhibitor would decrease disease pathogenesis in a lupus mouse model with established early disease. Additiona...
Article
Full-text available
Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE) causing morbidity and mortality in 40-60% of SLE patients. The pathogenic mechanisms of LN are not completely understood. Recent studies have demonstrated the presence of various immune cell populations in lupus nephritic kidneys of both SLE patients and lupus-prone...
Article
Full-text available
Background: Systemic lupus erythematosus, characterized by persistent inflammation, is a complex autoimmune disorder with no known cure. Immunosuppressants used in treatment put patients at a higher risk of infections. New knowledge of disease modulators, such as symbiotic bacteria, can enable fine-tuning of parts of the immune system, rather than...
Chapter
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The host’s genetic make-up is the primary factor in determining the composition of one’s adult microbiota. Other contributing factors include mother’s health in utero, the method of delivery during birth, if one is either breast fed or fed formula, the use of antibiotics during early childhood and types of foods consumed prior to, and during, weani...
Article
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The intestinal epithelial lining, together with factors secreted from it, forms a barrier that separates the host from the environment. In pathologic conditions, the permeability of the epithelial lining may be compromised allowing the passage of toxins, antigens, and bacteria in the lumen to enter the blood stream creating a “leaky gut.” In indivi...
Article
Lupus nephritis, a leading cause of morbidity and mortality in patients with Systemic Lupus Erythematosus (SLE), manifests as inflammatory infiltration of the kidney. Many types of leukocytes infiltrate the kidney during the progression of lupus nephritis, but the specific contributions of each infiltrating population are still unclear. In this stu...
Article
To date, there are 18 histone deacetylase (HDAC) enzymes, divided into four classes, which alter protein function by removing acetyl groups from lysine residues. Prior studies report that non-selective HDAC inhibitors decrease disease in lupus mouse models. Concern for adverse side effects of non-selective HDAC inhibition supports investigation of...
Article
Plasmacytoid dendritic cells (pDCs) are professional type I IFN producers believed to promote lupus. However, questions exist about whether they function at the same level throughout the course of lupus disease. We analyzed high-purity pDCs sorted from lupus mice. Although pDCs produced a large amount of IFN-α during disease initiation, those sorte...
Article
Full-text available
We sought to determine if a selective HDAC6 inhibitor (ACY-738) decreases disease in NZB/W mice. From 22 to 38weeks-of-age, mice were injected intraperitoneally with 5 or 20mg/kg of ACY-738, or vehicle control. Body weight and proteinuria were measured every 2weeks, while sera anti-dsDNA, Ig isotypes, and cytokine levels were measured every 4weeks....
Article
Full-text available
Plasmacytoid dendritic cells (pDCs) are professional type I IFN producers believed to promote lupus. However, questions exist about whether they function at the same level throughout the course of lupus disease. We analyzed high-purity pDCs sorted from lupus mice. Although pDCs produced a large amount of IFN-α during disease initiation, those sorte...
Article
Full-text available
Prior studies have shown that pan-HDAC inhibition can decrease disease in lupus mice; however, the mechanisms(s) remain to be elucidated. MRL/MpJ-Fas(lpr) (MRL/lpr) mice develop a lupus-like disease characterized by anti-dsDNA production, lymphoproliferation, and immune complex-mediated glomerulonephritis. Early- and late-disease (12 and 20weeks-of...
Poster
Poster presentation during the 11th International Congress on Systemic Lupus Erythematosus in Vienna, Austria
Article
To date, there are 17 histone deacetylase (HDAC) enzymes, divided into 4 classes, which alter protein function by removing acetyl groups from lysine residues. Prior studies report that non-selective HDAC inhibitors decrease disease in various lupus mouse models. Selective HDAC-6 inhibition acts on cytosolic proteins to decrease B cell proliferation...
Article
Full-text available
Therapeutic inhibition of histone deacetylase (HDAC) enzymes has been widely reported for the treatment of many cancers. Recently, increasing evidence of HDACs playing a role in regulating inflammation and immunity has triggered more in-depth investigations on how pharmacologic HDAC inhibitors could be beneficial in treating inflammatory and autoim...
Article
Conjugated linoleic acid (CLA) has been shown to reduce inflammation via Peroxisome Proliferator-Activated Receptor (PPAR)-γ in inflammatory disorders. We sought to determine whether CLA isomers would reduce inflammation via PPARγ in cultured mesangial cells, and in murine autoimmune glomerulonephritis. Mesangial cells were cultured with pure CLA i...
Article
Histone deacetylase inhibitors are important modifiers of gene and protein expression. In our studies, we sought to determine if a specific HDAC6 inhibitor (ACY-738) was able to decrease disease in NZB/W lupus-prone mice through regulation of B and T cell differentiation. From 22 - 38 weeks-of-age, NZB/W mice were injected intraperitoneally with 20...
Article
We sought to determine if a specific class I and II HDAC inhibitor (ITF2357) was able to decrease disease in lupus-prone NZB/W mice through regulation of T cell profiles. From 22 to 38weeks-of-age, NZB/W and non-lupus NZW mice were treated with ITF2357 (5mg/kg or 10mg/kg), or vehicle control. Body weight and proteinuria were measured every 2weeks,...
Article
Full-text available
Despite the tremendous success of cisplatin and other platinum-based anticancer drugs, severe toxicity and resistance to tumors limit their applications. It is believed that the coordination (formation of covalent bond) of the metal (platinum) to the nitrogen bases of DNA cause the ruptures of the cancer as well as normal cells. A search for antica...
Article
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Aim: To study the efficacy of novel rhenium compounds to treat triple node negative breast cancer. Place and duration: Six (6) novel rhenium pentycarbanato compounds (PC1-6) were synthesized and triple node negative breast cancer cell lines HTB-132 and Balb/c mouse kidney cell lines were treated with each of them for 48 hours. The results were a...
Article
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Epigenetic factors, including altered microRNA (miRNA) expression, may contribute to aberrant immune cell function in systemic lupus erythematosus (SLE). MiRNA-let-7a (let-7a) has been shown to directly alter cell cycle progression and proinflammatory cytokine production. Due to the crucial role of let-7a in cell division and inflammation, we inves...
Article
Determining alterations to disease-associated miRNAs induced by specific therapeutics may allow the use of tailored therapy in lupus. We determined miRNA alterations in female NZB/W lupus mice treated with hydroxychloroquine (HCQ) or prednisone (PRED) for 12weeks beginning at 24weeks-of-age. B cell, PBMC, and urinary miR-let-7a expression were decr...
Article
Full-text available
Cerium oxide nanoparticles (nanoceria) possess catalytic and regenerative radical scavenging activities. The ability of nanoceria to maintain cellular redox balance makes them ideal candidates for treatment of retinal diseases whose development is tightly associated with oxidative damage. We have demonstrated that our stable water-dispersed nanocer...
Article
Abstract Recent evidence supports a role for epigenetic alterations in the pathogenesis of systemic lupus erythematosus (SLE). MicroRNAs (miRNAs or miRs) are endogenous epigenetic regulators whose expression is altered in many diseases, including SLE. IL-6 is an inflammatory cytokine produced by mesangial cells during lupus nephritis (LN). IL-6 con...
Article
Full-text available
Immunomodulation by nanoparticles, especially as related to the biochemical properties of these unique materials, has scarcely been explored. In an in vitro model of human immunity, we demonstrate two catalytic nanoparticles, TiO2 (oxidant) and CeO2 (antioxidant), have nearly opposite effects on human dendritic cells and T helper (TH) cells. For ex...
Data
Endotoxin levels of CeO2 and TiO2 NP measured <0.05 EU/mL. The TiO2 and CeO2 NPs were diluted to 100 µM concentrations in sterile endotoxin-free water. The diluted preparations were then examined for endotoxin levels using an automated FDA-licensed endotoxin detection system by Charles Rivers Laboratories. No detectable (ND) levels of endotoxin wer...
Data
CeO2 mediates cellular stress induced by mitogen control as indicated by reduced CD95 expression. Freshly isolated CD4+ T cells were cultured in the absence or presence of TiO2 NPs (1 µM), CeO2 NPs (1 µM), PHA/PMA (as a positive assay control), or combinations of either NP with PHA/PMA. After 5 days, the cultures were harvested and stained with ant...
Data
T cells remain viable following treatment with NPs. Freshly isolated CD4+ T cells were cultured in the absence or presence of TiO2 NPs (1 µM), CeO2 NPs (1 µM), PHA/PMA (as a positive assay control), or combinations of either NP with PHA/PMA. After 5 days, the cultures were harvested and stained with the viability dye (LDA) and examined by flow cyto...
Data
Statistical analysis of Figure 6 A. Tukey’s honest significance test was employed, in conjunction with an ANOVA, to determine if the treatment groups (between CeO2 and TiO2) are significantly different from each other in relation to CFSE fluorescence. (DOCX)
Data
Statistical analysis of Figure 6 B. As in Table S1, Tukey’s honest significance test was employed, in conjunction with an ANOVA, to determine if the treatment groups (between CeO2 and TiO2) are significantly different from each other in relation to CD25 expression. (DOCX)