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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

B Lymphocyte-Induced Maturation Protein-1 Contributes to Intestinal Mucosa Homeostasis by Limiting the Number of IL-17-Producing CD4(+) T Cells

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Salehi, Soofia [1, 2] ; Bankoti, Rashmi [1, 2] ; Benevides, Luciana [3, 1, 2] ; Witten, Jessica [1, 2] ; Couse, Michael [1, 2] ; Silva, Joao S. [3] ; Dhall, Deepti [4] ; Meffre, Eric [5] ; Targan, Stephan [1, 2, 6] ; Martins, Gistaine A. [1, 2, 6]
Total Authors: 10
[1] Cedars Sinai Med Ctr, Immunobiol Res Inst, Los Angeles, CA 90048 - USA
[2] F Widjaja Fdn Inflammatory Bowel, Los Angeles, CA 90048 - USA
[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Immunol & Biochem, BR-14049 Ribeirao Preto - Brazil
[4] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 - USA
[5] Yale Univ, Dept Immunobiol, New Haven, CT 06511 - USA
[6] Cedars Sinai Med Ctr, Dept Biomed Sci, Res Div Immunol, Los Angeles, CA 90048 - USA
Total Affiliations: 6
Document type: Journal article
Source: JOURNAL OF IMMUNOLOGY; v. 189, n. 12, p. 5682-5693, DEC 15 2012.
Web of Science Citations: 27

The transcription factor B lymphocyte induced maturation protein-1 (Blimp-1) plays important roles in embryonic development and immunity. Blimp-1 is required for the differentiation of plasma cells, and mice with T cell specific deletion of Blimp-1 (Blimp-1CKO mice) develop a fatal inflammatory response in the colon. Previous work demonstrated that lack of Blimp-1 in CD4(+) and CD8(+) T cells leads to intrinsic functional defects, but little is known about the functional role of Blimp-1 in regulating differentiation of Th cells in vivo and their contribution to the chronic intestinal inflammation observed in the Blimp1CKO mice. In this study, we show that Blimp-1 is required to restrain the production of the inflammatory cytokine IL-17 by Th cells in vivo. Blimp-1CKO mice have greater numbers of IL-17 producing TCR beta(+)CD4(+)cells in lymphoid organs and in the intestinal mucosa. The increase in IL-17 producing cells was not restored to normal levels in wild-type and Blimp-1CKO mixed bone marrow chimeric mice, suggesting an intrinsic role for Blimp-1 in constraining the production of IL-17 in vivo. The observation that Blimp-1 deficient CD4(+) T cells are more prone to differentiate into IL-17(+)/IFN-gamma(+) cells and cause severe colitis when transferred to Rag1-deficient mice provides further evidence that Blimp-1 represses IL-17 production. Analysis of Blimp-1 expression at the single cell level during Th differentiation reveals that Blimp-1 expression is induced in Th1 and Th2 but repressed by TGF-beta in Th17 cells. Collectively, the results described here establish a new role for Blimp-1 in regulating IL-17 production in vivo. The Journal of Immunology, 2012,189: 5682-5693. (AU)

FAPESP's process: 08/04606-2 - CD4+CD25+ T regulatory and Th17 cells in immunity to breast tumour
Grantee:Luciana Benevides
Support Opportunities: Scholarships in Brazil - Doctorate