Reference - Detail
| RRC ID | 54505 |
|---|---|
| Author | Kobayashi S, Watanabe T, Suzuki R, Furu M, Ito H, Ito J, Matsuda S, Yoshitomi H. |
| Title | TGF-β induces the differentiation of human CXCL13-producing CD4(+) T cells. |
| Journal | Eur J Immunol |
| Abstract |
In the ectopic lymphoid-like structures present in chronic inflammatory conditions such as rheumatoid arthritis, a subset of human effector memory CD4(+) T cells that lacks features of follicular helper T (Tfh) cells produces CXCL13. Here, we report that TGF-β induces the differentiation of human CXCL13-producing CD4(+) T cells from naïve CD4(+) T cells. The TGF-β-induced CXCL13-producing CD4(+) T cells do not express CXCR5, B-cell lymphoma 6 (BCL6), and other Tfh-cell markers. Furthermore, expression levels of CD25 (IL-2Rα) in CXCL13-producing CD4(+) T cells are significantly lower than those in FoxP3(+) in vitro induced Treg cells. Consistent with this, neutralization of IL-2 and knockdown of STAT5 clearly upregulate CXCL13 production by CD4(+) T cells, while downregulating the expression of FoxP3. Furthermore, overexpression of FoxP3 in naïve CD4(+) T cells downregulates CXCL13 production, and knockdown of FoxP3 fails to inhibit the differentiation of CXCL13-producing CD4(+) T cells. As reported in rheumatoid arthritis, proinflammatory cytokines enhance secondary CXCL13 production from reactivated CXCL13-producing CD4(+) T cells. Our findings demonstrate that CXCL13-producing CD4(+) T cells lacking Tfh-cell features differentiate via TGF-β signaling but not via FoxP3, and exert their function in IL-2-limited but TGF-β-rich and proinflammatory cytokine-rich inflammatory conditions. |
| Volume | 46(2) |
| Pages | 360-71 |
| Published | 2016-2-1 |
| DOI | 10.1002/eji.201546043 |
| PMID | 26541894 |
| PMC | PMC5063156 |
| MeSH | Adolescent Adult Animals Arthritis, Rheumatoid / immunology* Cell Differentiation Cells, Cultured Chemokine CXCL13 / metabolism* Child Child, Preschool Female Gene Expression Regulation Humans Inflammation Mediators / metabolism Male Mice Middle Aged T-Lymphocyte Subsets / immunology* T-Lymphocytes, Helper-Inducer / immunology* Transforming Growth Factor beta / immunology* Young Adult |
| IF | 4.695 |
| Times Cited | 21 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 11 |
| Altmetric score changes over past 6months | 3.0 |
| Resource | |
| DNA material | CSII-EF-MCS-IRES2-Venus (RDB04384) CS-RfA-EG (RDB04391) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394) CSII-EF-IRES2-Venus_hFoxP3 (RDB17320) CSU6EG_sh7T-hFoxP3 (RDB17321) CSU6EG_sh2-hSTAT5AB (RDB17322) |