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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: JOURNAL OF IMMUNOLOGY; v. 189, n. 12, p. 5682-5693, DEC 15 2012.
• Web of Science Citations: 27

Abstract

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