Transcription Factor STAT3 and Type I Interferons Are Corepressive Insulators for Differentiation of Follicular Helper and T Helper 1 Cells

被引：199

作者：

Ray, John P. ^{[1
]}

Marshall, Heather D. ^{[1
]}

Laidlaw, Brian J. ^{[1
]}

Staron, Matthew M. ^{[1
]}

Kaech, Susan M. ^{[1
,2
]}

Craft, Joe ^{[1
,3
]}

机构：

[1] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA

[2] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[3] Yale Univ, Sch Med, Dept Med Rheumatol, New Haven, CT 06520 USA

来源：

IMMUNITY | 2014年 / 40卷 / 03期

基金：

美国国家科学基金会;

关键词：

CD4; T-CELLS; CENTER B-CELL; CUTTING EDGE; BCL6; EFFECTOR; IL-21; GENERATION; EXPRESSION; MUTATIONS; INDUCTION;

D O I：

10.1016/j.immuni.2014.02.005

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Follicular helper T (Tfh) cells are required for the establishment of T-dependent B cell memory and high affinity antibody-secreting cells. We have revealed herein opposing roles for signal transducer and activator of transcription 3 (STAT3) and type I interferon (IFN) signaling in the differentiation of Tfh cells following viral infection. STAT3-deficient CD4(+) T cells had a profound defect in Tfh cell differentiation, accompanied by decreased germinal center (GC) B cells and antigen-specific antibody production during acute infection with lymphocytic choriomeningitis virus. STAT3-deficient Tfh cells had strikingly increased expression of a number of IFN-inducible genes, in addition to enhanced T-bet synthesis, thus adopting a T helper 1 (Th1) cell-like effector phenotype. Conversely, IFN-alpha beta receptor blockade restored Tfh and GC B cell phenotypes in mice containing STAT3-deficient CD4(+) T cells. These data suggest mutually repressive roles for STAT3 and type I IFN signaling pathways in the differentiation of Tfh cells following viral infection.

引用

页码：367 / 377

页数：11

共 51 条

[1] STRATEGIES OF ANTICYTOKINE MONOCLONAL-ANTIBODY DEVELOPMENT - IMMUNOASSAY OF IL-10 AND IL-5 IN CLINICAL-SAMPLES [J].

ABRAMS, JS ;

RONCAROLO, MG ;

YSSEL, H ;

ANDERSSON, U ;

GLEICH, GJ ;

SILVER, JE .

IMMUNOLOGICAL REVIEWS, 1992, 127 :5-24

[2] IL-27 supports germinal center function by enhancing IL-21 production and the function of T follicular helper cells [J].

Batten, Marcel ;

Ramamoorthi, Nandhini ;

Kljavin, Noelyn M. ;

Ma, Cindy S. ;

Cox, Jennifer H. ;

Dengler, Hart S. ;

Danilenko, Dimitry M. ;

Caplazi, Patrick ;

Wong, Melanie ;

Fulcher, David A. ;

Cook, Matthew C. ;

King, Cecile ;

Tangye, Stuart G. ;

de Sauvage, Frederic J. ;

Ghilardi, Nico .

JOURNAL OF EXPERIMENTAL MEDICINE, 2010, 207 (13) :2895-2906

[3] Cutting Edge: STAT1 Is Required for IL-6-Mediated Bcl6 Induction for Early Follicular Helper Cell Differentiation [J].

Choi, Youn Soo ;

Eto, Danelle ;

Yang, Jessica A. ;

Lao, Christopher ;

Crotty, Shane .

JOURNAL OF IMMUNOLOGY, 2013, 190 (07) :3049-3053

[4] ICOS Receptor Instructs T Follicular Helper Cell versus Effector Cell Differentiation via Induction of the Transcriptional Repressor BcI6 [J].

Choi, Youn Soo ;

Kageyama, Robin ;

Eto, Danello ;

Escobar, Tania C. ;

Johnston, Robert J. ;

Monticelli, Laurel ;

Lao, Christopher ;

Crotty, Shane .

IMMUNITY, 2011, 34 (06) :932-946

[5] Initial Clonal Expansion of Germinal Center B Cells Takes Place at the Perimeter of Follicles [J].

Coffey, Francis ;

Alabyev, Boris ;

Manser, Tim .

IMMUNITY, 2009, 30 (04) :599-609

[6] Follicular helper T cells in immunity and systemic autoimmunity [J].

Craft, Joseph E. .

NATURE REVIEWS RHEUMATOLOGY, 2012, 8 (06) :337-347

[7] Follicular Helper CD4 T Cells (TFH) [J].

Crotty, Shane .

ANNUAL REVIEW OF IMMUNOLOGY, VOL 29, 2011, 29 :621-663

[8] An Interleukin-21-Interleukin-10-STAT3 Pathway Is Critical for Functional Maturation of Memory CD8+ T Cells [J].

Cui, Weiguo ;

Liu, Ying ;

Weinstein, Jason S. ;

Craft, Joseph ;

Kaech, Susan M. .

IMMUNITY, 2011, 35 (05) :792-805

[9] Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells [J].

de Beaucoudrey, Ludovic ;

Puel, Anne ;

Filipe-Santos, Orchidee ;

Cobat, Aurelie ;

Ghandil, Pegah ;

Chrabieh, Maya ;

Feinberg, Jacqueline ;

von Bernuth, Horst ;

Samarina, Arina ;

Janniere, Lucile ;

Fieschi, Claire ;

Stephan, Jean-Louis ;

Boileau, Catherine ;

Lyonnet, Stanislas ;

Jondeau, Guillaume ;

Cormier-Daire, Valerie ;

Le Merrer, Martine ;

Hoarau, Cyrille ;

Lebranchu, Yvon ;

Lortholary, Olivier ;

Chandesris, Marie-Olivia ;

Tron, Francois ;

Gambineri, Eleonora ;

Bianchi, Lucia ;

Rodriguez-Gallego, Carlos ;

Zitnik, Simona E. ;

Vasconcelos, Julia ;

Guedes, Margarida ;

Vitor, Artur Bonito ;

Marodi, Laszlo ;

Chapel, Helen ;

Reid, Brenda ;

Roifman, Chaim ;

Nadal, David ;

Reichenbach, Janine ;

Caragol, Isabel ;

Garty, Ben-Zion ;

Dogu, Figen ;

Camcioglu, Yildiz ;

Gulle, Sanyie ;

Sanal, Ozden ;

Fischer, Alain ;

Abel, Laurent ;

Stockinger, Birgitta ;

Picard, Capucine ;

Casanova, Jean-Laurent .

JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (07) :1543-1550

[10] IL-21 and IL-6 Are Critical for Different Aspects of B Cell Immunity and Redundantly Induce Optimal Follicular Helper CD4 T Cell (Tfh) Differentiation [J].

Eto, Danelle ;

Lao, Christopher ;

DiToro, Daniel ;

Barnett, Burton ;

Escobar, Tania C. ;

Kageyama, Robin ;

Yusuf, Isharat ;

Crotty, Shane .

PLOS ONE, 2011, 6 (03)

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