Leptin deficiency down-regulates IL-23 production in glomerular podocytes resulting in an attenuated immune response in nephrotoxic serum nephritis
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 murin...
Source: International Immunology - March 30, 2016 Category: Allergy & Immunology Authors: Goto, K., Kaneko, Y., Sato, Y., Otsuka, T., Yamamoto, S., Goto, S., Yamamoto, K., Yamamoto, T., Kawachi, H., Madaio, M. P., Narita, I. Tags: Original Research Source Type: research
Therapeutic potential of regulatory cytokines that target B cells
Autoreactive B cells play a crucial role in the pathogenesis of autoimmune diseases by producing auto-antibodies and presenting antigens. Regulatory cytokines that simultaneously suppress multiple pathways have the potential to control autoreactive B cells. The generally inhibitory cytokine IL-10 may have a stimulatory effect on human B-cell survival and antibody production. TGF-β family cytokines can decrease or increase antibody production and can suppress B-cell proliferation and differentiation. In contrast to TGF-β1, which induces extensive fibrosis, TGF-β3 and bone morphogenetic protein 6 (BMP-6)/BMP-7...
Source: International Immunology - March 30, 2016 Category: Allergy & Immunology Authors: Fujio, K., Okamura, T., Sumitomo, , S., Yamamoto, K. Tags: Invited review Source Type: research
Therapeutic antibodies that target inflammatory cytokines in autoimmune diseases
Inflammatory cytokines are key regulators of immune responses. Persistent and excessive production of inflammatory cytokines underscores the development of autoimmune diseases. Therefore, neutralizing inflammatory cytokines or antagonizing their receptor function is considered as a useful therapeutic strategy to treat autoimmune diseases. To achieve the success of such a strategy, understanding of the complex actions of these cytokines and cytokine networks is required. In this review we focus on four inflammatory cytokines—tumor necrosis factor α (TNFα), interleukin-6 (IL-6), IL-23 and IL-17—and di...
Source: International Immunology - March 30, 2016 Category: Allergy & Immunology Authors: Lai, Y., Dong, C. Tags: Invited review Source Type: research
T follicular helper cells, T follicular regulatory cells and autoimmunity
CD4+ T follicular helper (Tfh) cells are recognized as a distinct T-cell subset, which provides help for germinal center (GC) formation, B-cell development and affinity maturation, and immunoglobulin class switching, as an indispensable part of adaptive immunity. Tfh cell differentiation depends on various factors including cell-surface molecule interactions, extracellular cytokines and multiple transcription factors, with B-cell lymphoma 6 (Bcl-6) being the master regulator. T follicular regulatory (Tfr) cells are also located in the GC and share phenotypic characteristics with Tfh cells and regulatory T cells, but functi...
Source: International Immunology - March 30, 2016 Category: Allergy & Immunology Authors: Zhu, Y., Zou, L., Liu, Y.-C. Tags: Invited review Source Type: research
CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm
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 ...
Source: International Immunology - March 30, 2016 Category: Allergy & Immunology Authors: Hirahara, K., Nakayama, T. Tags: Invited review Source Type: research
Genetics of autoimmune diseases: perspectives from genome-wide association studies
Genome-wide association studies (GWASs) 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 are often cell type-specific, the incorporation of epigenetic data from disease-related ...
Source: International Immunology - March 30, 2016 Category: Allergy & Immunology Authors: Kochi, Y. Tags: Invited review Source Type: research
Introduction: Autoimmunity Special Issue
(Source: International Immunology)
Source: International Immunology - March 30, 2016 Category: Allergy & Immunology Authors: Yamamoto, K. Tags: Introduction Source Type: research
Table of Contents
(Source: International Immunology)
Source: International Immunology - March 30, 2016 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research
Subscriptions
(Source: International Immunology)
Source: International Immunology - March 30, 2016 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research
Cover
(Source: International Immunology)
Source: International Immunology - March 30, 2016 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research
Vitamin A deficient mice exhibit increased viral antigens and enhanced cytokine/chemokine production in nasal tissues following respiratory virus infection despite the presence of FoxP3+ T cells
The World Health Organization (WHO) estimates that 250 million children under the age of five suffer from vitamin A deficiencies (VAD). Individuals with VAD experience higher rates of mortality and increased morbidity during enteric and respiratory infections compared with those who are vitamin A sufficient. Previously, our laboratory has demonstrated that VAD mice have significantly impaired virus-specific IgA and CD8+ T-cell responses in the airways. Here, we demonstrate that VAD mice experience enhanced cytokine/chemokine gene expression and release in the respiratory tract 10 days following virus infection compared wit...
Source: International Immunology - February 23, 2016 Category: Allergy & Immunology Authors: Penkert, R. R., Surman, S. L., Jones, B. G., Sealy, R. E., Vogel, P., Neale, G., Hurwitz, J. L. Tags: Original Research Source Type: research
CD3{varepsilon} recruits Numb to promote TCR degradation
Modulation of TCR signaling upon ligand binding is achieved by changes in the equilibrium between TCR degradation, recycling and synthesis; surprisingly, the molecular mechanism of such an important process is not fully understood. Here, we describe the role of a new player in the mediation of TCR degradation: the endocytic adaptor Numb. Our data show that Numb inhibition leads to abnormal intracellular distribution and defective TCR degradation in mature T lymphocytes. In addition, we find that Numb simultaneously binds to both Cbl and a site within CD3 that overlaps with the Nck binding site. As a result, Cbl couples spe...
Source: International Immunology - February 23, 2016 Category: Allergy & Immunology Authors: Martin-Blanco, N., Jimenez Teja, D., Bretones, G., Borroto, A., Caraballo, M., Screpanti, I., Leon, J., Alarcon, B., Canelles, M. Tags: Original Research Source Type: research
Strong TCR-mediated signals suppress integrated stress responses induced by KDELR1 deficiency in naive T cells
KDEL receptor 1 (KDELR1) regulates integrated stress responses (ISR) to promote naive T-cell survival in vivo. In a mouse line having nonfunctional KDELR1, T-Red (naive T-cell reduced) mice, polyclonal naive T cells show excessive ISR and eventually undergo apoptosis. However, breeding T-Red mice with TCR-transgenic mice bearing relatively high TCR affinity rescued the T-Red phenotype, implying a link between ISR-induced apoptosis and TCR-mediated signaling. Here, we showed that strong TCR stimulation reduces ISR in naive T cells. In mice lacking functional KDELR1, surviving naive T cells expressed significantly higher lev...
Source: International Immunology - February 23, 2016 Category: Allergy & Immunology Authors: Kamimura, D., Arima, Y., Tsuruoka, M., Jiang, J.-j., Bando, H., Meng, J., Sabharwal, L., Stofkova, A., Nishikawa, N., Higuchi, K., Ogura, H., Atsumi, T., Murakami, M. Tags: featured content Source Type: research
TANK-binding kinase 1-dependent or -independent signaling elicits the cell-type-specific innate immune responses induced by the adenovirus vector
In this study, to determine the impacts of viral nucleic acids on innate immune responses in vivo, we administered transgene-expressing Adv to Tbk1-deficient mice. The systemic Adv administration failed to induce type I interferons (type I IFNs) in the spleen, but not the liver, of Tbk1-deficient mice, resulting in the increase of transgene-expressing cells in the spleen, but not the liver. Moreover, Adv failed to induce type I IFNs in the bone-marrow-derived dendritic cells, but not the mouse embryonic fibroblasts, from Tbk1-deficient mice in vitro. These results support the idea that Adv elicit innate immunity in immune ...
Source: International Immunology - February 23, 2016 Category: Allergy & Immunology Authors: Tsuzuki, S., Tachibana, M., Hemmi, M., Yamaguchi, T., Shoji, M., Sakurai, F., Kobiyama, K., Kawabata, K., Ishii, K. J., Akira, S., Mizuguchi, H. Tags: Original Research Source Type: research
In This Issue
(Source: International Immunology)
Source: International Immunology - February 23, 2016 Category: Allergy & Immunology Tags: In This Issue Source Type: research
