International Immunology (INT IMMUNOL)
International Immunology publishes a broad range of experimental and theoretical studies in molecular and cellular immunology conducted in laboratories throughout the world.
Current impact factor: 2.54
Impact Factor Rankings
|2016 Impact Factor||Available summer 2017|
|2014 / 2015 Impact Factor||2.536|
|2013 Impact Factor||3.181|
|2012 Impact Factor||3.135|
|2011 Impact Factor||3.415|
|2010 Impact Factor||3.301|
|2009 Impact Factor||3.403|
|2008 Impact Factor||3.181|
|2007 Impact Factor||3.29|
|2006 Impact Factor||4.015|
|2005 Impact Factor||3.317|
|2004 Impact Factor||3.543|
|2003 Impact Factor||3.69|
|2002 Impact Factor||3.595|
|2001 Impact Factor||3.611|
|2000 Impact Factor||3.13|
|1999 Impact Factor||2.897|
|1998 Impact Factor||3.188|
|1997 Impact Factor||3.548|
|1996 Impact Factor||4.485|
|1995 Impact Factor||4.333|
|1994 Impact Factor||4.185|
|1993 Impact Factor||3.954|
|1992 Impact Factor||3.841|
Impact factor over time
|Website||International Immunology website|
|Other titles||International immunology online., International immunology|
|Material type||Periodical, Internet resource|
|Document type||Journal / Magazine / Newspaper, Internet Resource|
- Author can archive a pre-print version
- Author cannot archive a post-print version
- 12 months embargo
- Pre-print can only be posted prior to acceptance
- Pre-print must be accompanied by set statement (see link)
- Pre-print must not be replaced with post-print, instead a link to published version with amended set statement should be made
- Pre-print on author's personal website, employer website, free public server or pre-prints in subject area
- Post-print in Institutional repositories or Central repositories
- Publisher's version/PDF cannot be used
- Published source must be acknowledged
- Must link to publisher version
- Set phrase to accompany archived copy (see policy)
- Eligible authors may deposit in OpenDepot
- The publisher will deposit in PubMed Central on behalf of NIH authors
- Publisher last contacted on 19/02/2015
- This policy is an exception to the default policies of 'Oxford University Press (OUP)'
Publications in this journal
- [Show abstract] [Hide abstract] ABSTRACT: Immunotherapy has received the expectation that it should contribute to the therapy of cancer patients for more than a hundred years. At long last, recent clinical trials of immunotherapy with immune checkpoint inhibitors as well as adoptive cell therapy with genetically engineered T cells have reported their remarkable efficacies. Nowadays, it is expected that T-cell adoptive immunotherapy can not only control tumor progression but even cure cancer in some patients. On the other hand, severe adverse events associated with efficacy have frequently been reported in clinical trials, suggesting that the assessment and control of safety will be indispensable in the future development of the therapy. New approaches in T-cell adoptive immunotherapy such as reduction of adverse events, targeting of new antigens, or utilization of allogeneic cells will open a new gate for less harmful and more effective immunological treatment of cancer patients.
- [Show abstract] [Hide abstract] ABSTRACT: GYF-17, a 2-(2-phenethyl)-chromone derivative, was isolated from agarwood and showed superior activity of inhibiting NO production of RAW264.7 cells induced by LPS in our preliminary pharmacodynamic screening. In order to develop novel therapeutic drug for acute and chronic inflammatory disorders, the anti-inflammatory activity and underlying mechanism of GYF-17 were investigated in LPS-induced RAW264.7 cells. The results showed that GYF-17 could reduce LPS-induced expression of iNOS and then result in the decrement of NO production. More meaningful, the expression and secretion of key pro-inflammatory factors, including TNF-α, IL-6 and IL-1β, were intensively inhibited by GYF-17. Furthermore, GYF-17 also down regulated the expression of COX2 and the production of PGE2 which plays important role in causing algesthesia during inflammatory response. In mechanism study, GYF-17 selectively suppressed phosphorylation of STAT1/3 and ERK1/2 during the activation of NF-κB, MAPK and STAT signaling pathways induced by LPS. Collectively, GYF-17 can intensively suppress the production of LPS-induced inflammatory mediators in RAW264.7 cells by inhibiting STAT1/3 and ERK1/2 signaling pathways and thereby shows great potential to be developed into therapeutic drug for inflammatory diseases.
- [Show abstract] [Hide abstract] ABSTRACT: Recent studies have shown that tumor cells acquire escape mechanisms to evade host immunity in the tumor microenvironment. Two key immune checkpoint pathways mediated by immunosuppressive co-signaling, the first via programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-1/PD-L1) and the second via cytotoxic T cell lymphocyte antigen 4 (CTLA-4) and B7 (CTLA-4/B7), have been previously described. Several clinical trials have revealed an outstanding anti-tumor efficacy of immune checkpoint inhibitors (anti-CTLA-4 antibody, anti-PD-1 antibody and/or anti-PD-L1 antibody) in patients with various types of solid malignancies, including non-small cell lung cancer, melanoma, renal cell cancer and ovarian cancer. In this review, we examine pre-clinical studies that described the local immune status and immune checkpoint signals in ovarian cancer, highlight recent clinical trials that evaluated immune checkpoint inhibitors against ovarian cancer, and discuss the clinical issues regarding immune checkpoint inhibitors.
- [Show abstract] [Hide abstract] ABSTRACT: Chimeric antigen-receptors (CARs) are engineered molecules designed to endow a polyclonal T cell population with the ability to recognize tumor-associated surface antigens. In their simplest form, CARs comprise a targeting moiety in the form of a single-chain variable fragment (scFv) from an antibody connected to various intracellular signaling domains allowing for T cell activation. This powerful approach combines the specificity of an antibody with the cytotoxic ability of a T cell. There has been much excitement since early phase trials of CAR-T cells targeting CD19 expressed on B cell malignancies demonstrated remarkable efficacy in inducing long-term, stable remissions in otherwise relapsed/refractory disease. Despite these successes, we have just begun to understand the intricacies of CAR biology with efforts underway to utilize this platform in the treatment of other, previously refractory malignancies. Challenges currently include identification of viable cancer targets, management strategies for potentially severe and irreversible toxicities, and overcoming the immunosuppressive nature of the tumor microenvironment. This review will focus on basic CAR structure and function, previous success and new approaches aimed at the broader application of CAR-T cell therapy.
- [Show abstract] [Hide abstract] ABSTRACT: Accumulated evidence obtained from various clinical trials and animal studies suggested that cancer vaccines need better adjuvants than those that are currently licensed, which include the most commonly used alum and incomplete Freund’s adjuvant, because of either a lack of potent anti-tumor immunity or the induction of undesired immunity. Several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for TLRs, C-type lectin receptors, retinoic acid-inducible gene I-like receptors and stimulator of interferon genes, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy.
- [Show abstract] [Hide abstract] ABSTRACT: Checkpoint blockade therapy has been proven to be highly active across many cancer types but emerging evidence indicates that the therapeutic benefit is limited to a subset of patients in each cancer entity. The presence of CD8+ T cells within the tumor microenvironment or the invasive margin of the tumor, as well as the up-regulation of PD-L1, have emerged to be the most predictive biomarkers for clinical benefit in response to checkpoint inhibition. Although the up-regulation of immune inhibitory mechanisms is one mechanism of immune escape, commonly used by T-cell-inflamed tumors, exclusion of an anti-tumor specific T-cell infiltrate displays another even more potent mechanism of immune escape. This review will contrast the mechanisms of immunogenic, T-cell-inflamed, and the novel concept of non-immunogenic, non-T-cell-inflamed, adaptive immune escape.
- [Show abstract] [Hide abstract] ABSTRACT: Inflammatory responses contribute to host defense against harmful organisms and allergens, whereas a failure of immune tolerance can cause chronic inflammation including asthma. The lung has several innate myeloid cell subsets. Among these subsets, there are two types of macrophages: alveolar macrophages (AMs) and interstitial macrophages (IMs). However, compared with AMs, the role of IMs in lung homeostasis remains poorly understood. In this study, we characterized AMs and IMs in healthy and inflammatory conditions. Pulmonary IMs constitutively produce the anti-inflammatory cytokine IL-10 through activation of the TLR4/MyD88 pathway in a microbiota-independent manner. In addition to IMs, Foxp3+ Treg cells show persistent IL-10 expression in the lung, with IL-10-producing IMs more prevalent than Foxp3+ Treg cells. IMs, but not Foxp3+ Treg cells, increased IL-10 production in house dust mite- challenged mice, a model of human asthma. House dust mite-challenged Il10-/- mice exhibited severe lung pathology characterized by neutrophilia compared with that of wild-type mice. In addition, transplantation of wild-type IMs reduced neutrophilic inflammation, goblet cell mucus production, and decreased expression of lung IL-13 and Th17-related neutrophil-activating cytokines such as IL-17, GM-CSF, and TNF-α. Together, these results demonstrate that IL-10-producing IMs negatively regulate Th2- and Th17-mediated inflammatory responses, helping prevent neutrophilic asthma.
- [Show abstract] [Hide abstract] ABSTRACT: B lymphocytes play a role in inhibiting the immune response against certain tumors, but the underlying mechanisms are poorly understood. EMT-6 mammary tumors grow well in wild type (WT) mice but show reduced growth in B-cell deficient µ-/- BALB/c mice (BCDM). WT mice demonstrate extensive B cell infiltration into the tumor bed, reduced CD8+ T cell and CD49+ NK cell infiltration, and markedly reduced cytolytic T cell response relative to BCDM. Expression of LAP/TGF-β1, CD80, CD86 and PDL-1 is significantly increased in tumor infiltrating B cells (TIL-B) relative to splenic B cells. LAP/TGF-β1 expression on TIL-B progressively increased from 5.4±1.7% on d8 to 43.1±6.1% by d21 post tumor implantation. Co-culture of EMT-6 tumor cells with naïve B cells ex vivo generated B cells (EMT6-B) with a similar immunophenotype to TIL-B. Purified TIL-B, or in vitro generated EMT6-B suppressed CD4+, CD8+ and CD4+CD25- T cell proliferation, and Th1 cytokine secretion, and also suppressed purified NK cell proliferation in response to IL-15, compared to naïve splenic B cells. Acquired B regulatory function required direct tumor cell: B cell contact, and was partially reversed by antibody to TGF-β or PDL-1, leading to tumor rejection in vivo. B cell acquisition of a suppressive phenotype following tumor infiltration may result in profound inhibition of T cell anti-tumor response.
- [Show abstract] [Hide abstract] ABSTRACT: CD4+ T cells are crucial for directing appropriate immune responses during host defense and for the pathogenesis of inflammatory diseases. In addition to the classical biphasic model of differentiation of T-helper 1 (Th1) and Th2 cells, unexpected increases in the numbers of CD4+ T cell subsets, including Th17, Th9, T follicular-helper (Tfh) and T-regulatory (Treg) cells, have been recognized. In the present review, we focus on how these various T-helper cell subsets contribute to the pathogenesis of immune-mediated inflammatory diseases. In particular, we focus on multiple sclerosis, psoriasis and asthma as typical model diseases in which multiple T-helper cell subsets have recently been suggested to play a role. We will also discuss various unique subpopulations of T-helper cells that have been identified. First, we will introduce the heterogeneous T-helper cell subsets, which are classified by their simultaneous expression of multiple key transcription factors. We will also introduce different kinds of memory-type Th2 cells, which are involved in the pathogenesis of chronic type-2 immune related diseases. Finally, we will discuss the molecular mechanisms underlying the generation of the plasticity and heterogeneity of T-helper cell subsets. The latest progress in the study of T-helper cell subsets has forced us to reconsider the etiology of immune-mediated inflammatory diseases beyond the model based on the Th1/Th2 balance. To this end, we propose another model — the pathogenic T-helper population disease-induction model — as a possible mechanism for the induction and/or persistence of immune-mediated inflammatory diseases.
- [Show abstract] [Hide abstract] ABSTRACT: Thalidomide and its derivatives, collectively referred to as Immunomodulatory drugs (IMiDs), are effective inhibitors of inflammation and are known to inhibit TLR induced TNFα production. The identification of Cereblon as the receptor for these compounds has led to a rapid advancement in our understanding of IMiD properties, however, there remain no studies addressing the role of Cereblon in mediating the suppressive effect of IMiDs on TLR responses. Here, we developed Cereblon deficient mice using the CRISPR-Cas9 system. TLR induced cytokine responses were unaffected by Cereblon deficiency in vivo. Moreover, IMiD treatment inhibited cytokine production even in the absence of Cereblon. The IMiD induced suppression of cytokine production therefore occurs independently of Cereblon in mice. Further investigation revealed that IMiDs are potent inhibitors of TLR induced type-1 interferon production via suppression of the TRIF/IRF3 pathway. These data suggest that IMiDs may prove effective in the treatment of disorders characterised by the ectopic production of type-1 interferon. Significantly, these properties are mediated separately from Thalidomide’s teratogenic receptor, Cereblon. Thus, certain therapeutic properties of Thalidomide can be separated from its harmful side effects.
- [Show abstract] [Hide abstract] ABSTRACT: Genome-wide association studies (GWAS) for autoimmune diseases (ADs) have identified many risk loci and have provided insights into the etiology of each disease. Some of these loci, such as PTPN22, IL23R, and STAT4, are shared among different ADs, and the combination of risk loci may determine an individual’s susceptibility for a disease. The majority of GWAS loci are expression quantitative trait loci (eQTLs), where disease-causing variants regulate expression of neighboring (or sometimes distant) genes. Because the eQTL effects often are cell type-specific, the incorporation of epigenetic data from disease-related cell types and tissues is expected to refine the identification of causal variants. The cumulative eQTL effects in multiple genes may influence the activity or fate of immune cells, which in turn may affect the function of the immune system in individuals. In this paper, I review the etiology of ADs by focusing on important immune cells (Th1, Th17, and regulatory T-cells), important pathways (antigen receptor signaling and type I interferon signaling), and relevant genes identified in GWAS.
- [Show abstract] [Hide abstract] ABSTRACT: LL-37 is the only known member of the cathelicidin family of antimicrobial peptides in humans. In addition to its broad spectrum of antimicrobial activities, LL-37 can modulate various inflammatory reactions. We previously revealed that LL-37 suppresses the lipopolysaccharide (LPS)/ATP-induced pyroptosis of macrophages in vitro by both neutralizing the action of LPS and inhibiting the response of P2X7 (a nucleotide receptor) to ATP. Thus, in this study, we further evaluated the effect of LL-37 on pyroptosis in vivo using a cecal ligation and puncture (CLP) septic model. As a result, the intravenous administration of LL-37 improved the survival of the CLP septic mice. Interestingly, LL-37 inhibited the CLP-induced caspase-1 activation and pyroptosis of peritoneal macrophages. Moreover, LL-37 modulated the levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) both in the peritoneal fluids and sera, and suppressed the activation of peritoneal macrophages (as evidenced by the increase in the intracellular levels of IL-1β, IL-6 and TNF-α). Finally, LL-37 reduced the bacterial burdens both in peritoneal fluids and blood samples. Together these observations suggest that LL-37 improves the survival of CLP septic mice by possibly suppressing the pyroptosis of macrophages, and inflammatory cytokine production by activated macrophages as well as bacterial growth. Thus, the present findings imply that LL-37 can be a promising candidate for sepsis due to its multifunction based on the inhibition of pyroptosis, modulation of inflammatory cytokine production and antimicrobial activity.
- [Show abstract] [Hide abstract] ABSTRACT: The adaptive immune response is involved in the development and progression of atherosclerosis and IL-17A(+) cells play a role in this disease. While elevated number of CD4(+) IL-17A(+) (Th17) and IL-17A(+)TCRγδ(+) T cells are found within murine atherosclerotic aortas and human plaques, the mechanisms governing IL-17A(+) T cell migration to atherosclerotic lesions are unclear. The chemokine receptor CXCR6 is expressed on several T cell subsets and plays a pro-atherogenic role in atherosclerosis. Here, we used CXCR6-deficient (Cxcr6(GFP/GFP)) Apolipoprotein E-deficient (Apoe(-/-)) mice to investigate the involvement of CXCR6 in the recruitment IL-17A(+) T cells to atherosclerotic aortas. Flow cytometric analyses revealed reductions in Th17 and IL-17A(+)TCRγδ(+) T cells within aged Cxcr6(GFP/GFP)Apoe(-/-) aortas, in comparison with age matched Cxcr6(GFP/+)Apoe(-/-) aortas. While CXCR6-sufficient IL-17A(+) T cells efficiently migrated towards CXCL16, the migration of CXCR6-deficient IL-17A(+) T cells was abolished in transwell assays. Importantly, the recruitment of Cxcr6(GFP/GFP)Apoe(-/-) IL-17A(+) T cells into the aortas of Apoe(-/-) recipients was markedly reduced in short-term adoptive transfer experiments. Altogether these results demonstrate an important role of CXCR6 in the regulation of pathological Th17 and IL-17A(+)TCRγδ(+) T cell recruitment into atherosclerotic lesions.
- [Show abstract] [Hide abstract] ABSTRACT: Leptin, one of the typical adipokines, is reported to promote Th17 cell responses and to enhance production of proinflammatory cytokines. To clarify the role of leptin in the regulation of the IL-23/IL-17 axis and the development of kidney disease, we used a murine model of nephrotoxic serum (NTS) nephritis (NTN). Sheep NTS was administered in wild-type C57BL/6J mice and food-restricted, leptin-deficient C57BL/6J-ob/ob (FR-ob/ob) mice after preimmunization with sheep IgG. The profile of mRNA expression relevant to T helper lymphocytes in the kidneys was analyzed by quantitative real-time PCR (qRT–PCR). Cultured murine glomerular podocytes and peritoneal exudate macrophages (PEMs) were used to investigate the direct effect of leptin on IL-23 or MCP-1 production by qRT–PCR. Kidney injury and macrophage infiltration were significantly attenuated in FR-ob/ob mice 7 days after NTS injection. The Th17-dependent secondary immune response against deposited NTS in the glomeruli was totally impaired in FR-ob/ob mice because of deteriorated IL-17 and proinflammatory cytokine production including IL-23 and MCP-1 in the kidney. IL-23 was produced in glomerular podocytes in NTN mice and cultured murine glomerular podocytes produced IL-23 under leptin stimulation. MCP-1 production in PEMs was also promoted by leptin. Induction of MCP-1 expression was observed in PEMs regardless of Ob-Rb, and the leptin signal was transduced without STAT3 phosphorylation in PEMs. Leptin deficiency impairs the secondary immune response against NTS and down-regulates IL-23 production and Th17 responses in the NTN kidney, which is accompanied by decreased MCP-1 production and macrophage infiltration in the NTN kidney.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.