TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf

被引：13

作者：

Chang, Yinshui ^{[1
,2
]}

Bach, Luisa ^{[1
]}

Hasiuk, Marko ^{[3
,4
,5
]}

Wen, Lifen ^{[6
]}

Elmzzahi, Tarek ^{[6
,7
]}

Tsui, Carlson ^{[6
]}

Gutierrez-Melo, Nicolas ^{[1
]}

Steffen, Teresa ^{[1
]}

Utzschneider, Daniel T. ^{[6
]}

Raj, Timsse ^{[2
]}

Jost, Paul Jonas ^{[8
]}

Heink, Sylvia ^{[9
]}

Cheng, Jingyuan ^{[10
]}

Burton, Oliver T. ^{[11
]}

Zeitraeg, Julia ^{[2
]}

Alterauge, Dominik ^{[2
]}

Dahlstroem, Frank ^{[2
]}

Becker, Jennifer-Christin ^{[1
]}

Kastl, Melanie ^{[1
,12
]}

Symeonidis, Konstantinos ^{[13
]}

van Uelft, Martina ^{[14
]}

Becker, Matthias ^{[15
,16
,17
]}

Reschke, Sarah ^{[18
]}

Krebs, Stefan ^{[18
]}

Blum, Helmut ^{[18
]}

Abdullah, Zeinab ^{[13
]}

Paeschke, Katrin ^{[1
,12
]}

Ohnmacht, Caspar ^{[19
,20
]}

Neumann, Christian ^{[21
]}

Liston, Adrian ^{[11
]}

Meissner, Felix ^{[10
,22
]}

Korn, Thomas ^{[9
,23
]}

Hasenauer, Jan ^{[8
,24
,25
]}

Heissmeyer, Vigo ^{[2
,26
]}

Beyer, Marc ^{[7
,16
,17
]}

Kallies, Axel ^{[6
]}

Jeker, Lukas T. ^{[3
,4
,5
]}

Baumjohann, Dirk ^{[1
,2
]}

机构：

[1] Univ Bonn, Univ Hosp Bonn, Med Clin Oncol Hematol Immuno Oncol & Rheumatol 3, Venusberg Campus 1, D-53127 Bonn, Germany

[2] Ludwig Maximilians Univ Munchen, Inst Immunol, Fac Med, Biomed Ctr, Grosshaderner Str 9, D-82152 Martinsried, Germany

[3] Basel Univ Hosp, Dept Biomed, Hebelstr 20, CH-4031 Basel, Switzerland

[4] Univ Basel, Hhebelstr 20, CH-4031 Basel, Switzerland

[5] Basel Univ Hosp, Transplantat Immunol & Nephrol, Petersgraben 4, CH-4031 Basel, Switzerland

[6] Univ Melbourne, Peter Doherty Inst Infect & Immun, Melbourne, Vic 3000, Australia

[7] Deutsch Zentrum Neurodegenerat Erkrankungen DZNE, Immunogen & Neurodegenerat, Bonn, Germany

[8] Univ Bonn, Fac Math & Nat Sci, Bonn, Germany

[9] Tech Univ Munich, Inst Expt Neuroimmunol, Sch Med, D-81675 Munich, Germany

[10] Max Planck Inst Biochem, Expt Syst Immunol, Martinsried, Germany

[11] Univ Cambridge, Dept Pathol, Cambridge, England

[12] Univ Bonn, Univ Hosp Bonn, Dept Clin Chem & Clin Pharmacol, Venusberg Campus 1, D-53127 Bonn, Germany

[13] Univ Bonn, Univ Hosp Bonn, Inst Mol Med & Expt Immunol, Venusberg Campus 1, D-53127 Bonn, Germany

[14] Univ Bonn, Genom & Immunoregulat Life & Med Sci LIMES Inst, Bonn, Germany

[15] Deutsch Zentrum Neurodegenerat Erkrankungen DZNE, Syst Med, Bonn, Germany

[16] Deutsch Zentrum Neurodegenerat Erkrankungen DZNE, PRECISE Platform Single Cell Genom & Epigen, Bonn, Germany

[17] Univ Bonn, Bonn, Germany

[18] Ludwig Maximilians Univ Munchen, Gene Ctr, Lab Funct Genome Anal LAFUGA, Feodor Lynen Str 25, D-81377 Munich, Germany

[19] Tech Univ, Ctr Allergy & Environm ZAUM, Munich, Germany

[20] Helmholtz Ctr Munich, Munich, Germany

[21] Charite Univ Med Berlin, Dept Microbiol Infect Dis & Immunol, Berlin, Germany

[22] Univ Bonn, Inst Innate Immun, Med Fac, Dept Syst Immunol & Prote, Bonn, Germany

[23] Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany

[24] Tech Univ Munich, Ctr Math, Garching, Germany

[25] Helmholtz Zentrum Munchen, Inst Computat Biol, Neuherberg, Germany

[26] Helmholtz Zentrum Munchen, Res Unit Mol Immune Regulat, Feodor Lynen Str 21, D-81377 Munich, Germany

来源：

SCIENCE IMMUNOLOGY | 2024年 / 9卷 / 93期

基金：

欧洲研究理事会; 英国惠康基金; 瑞士国家科学基金会;

关键词：

FOLLICULAR-HELPER-CELLS; TRANSCRIPTION FACTOR; HIGHLY EFFICIENT; BCL6; EXPRESSION; IN-VIVO; B-CELLS; DIFFERENTIATION; GENE; IL-21; GENERATION;

D O I：

10.1126/sciimmunol.add4818

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

T follicular helper (T-FH) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse T-FH cells has long been hampered by the lack of a reliable protocol for their generation in vitro. We report that transforming growth factor-beta (TGF-beta) induces robust expression of T-FH hallmark molecules CXCR5 and Bcl6 in activated mouse CD4(+) T cells in vitro. TGF-beta-induced mouse CXCR5(+) T-FH cells are phenotypically, transcriptionally, and functionally similar to in vivo-generated T-FH cells and provide critical help to B cells. The study further reveals that TGF-beta-induced CXCR5 expression is independent of Bcl6 but requires the transcription factor c-Maf. Classical TGF-beta-containing T helper 17 (T(H)17)-inducing conditions also yield separate CXCR5(+) and IL-17A-producing cells, highlighting shared and distinct cell fate trajectories of T-FH and T(H)17 cells. We demonstrate that excess IL-2 in high-density T cell cultures interferes with the TGF-beta-induced T-FH cell program, that T-FH and T(H)17 cells share a common developmental stage, and that c-Maf acts as a switch factor for T-FH versus T(H)17 cell fates in TGF-beta-rich environments in vitro and in vivo.

引用

页数：19

共 108 条

[1] TGFβ signaling in germinal center B cells promotes the transition from light zone to dark zone [J].