LEF-1 and TCF-1 orchestrate TFH differentiation by regulating differentiation circuits upstream of the transcriptional repressor BcI6

被引:262
作者
Choi, Youn Soo [1 ]
Gullicksrud, Jodi A. [2 ,3 ]
Xing, Shaojun [2 ]
Zeng, Zhouhao [4 ]
Shan, Qiang [2 ]
Li, Fengyin [2 ]
Love, Paul E. [5 ]
Peng, Weiqun [4 ]
Xue, Hai-Hui [2 ,3 ]
Crotty, Shane [1 ]
机构
[1] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA USA
[2] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA
[3] Univ Iowa, Carver Coll Med, Interdisciplinary Immunol Grad Program, Iowa City, IA USA
[4] George Washington Univ, Dept Phys, Washington, DC 20052 USA
[5] NICHD, Sect Cellular & Dev Biol, NIH, Bethesda, MD USA
基金
美国国家卫生研究院;
关键词
FOLLICULAR HELPER-CELL; B-CELLS; ICOS; BCL6; CD4(+); GENERATION; T-HELPER-1; FATE; INDUCTION; PROMOTE;
D O I
10.1038/ni.3226
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 cells (T-FH cells) are specialized effector CD4(+) T cells that help B cells develop germinal centers (GCs) and memory. However, the transcription factors that regulate the differentiation of T-FH cells remain incompletely understood. Here we report that selective loss of Lef1 or Tcf7 (which encode the transcription factor LEF-1 or ICE-1, respectively) resulted in T-FH cell defects, while deletion of both Lef1 and Tcf7 severely impaired the differentiation of T-FH cells and the formation of GCs. Forced expression of LEE-1 enhanced T-FH differentiation. LEF-1 and TCF-1 coordinated such differentiation by two general mechanisms. First, they established the responsiveness of naive CD4(+) T cells to T-FH cell signals. Second, they promoted early T-FH differentiation via the multipronged approach of sustaining expression of the cytokine receptors IL-61R alpha and gp130, enhancing expression of the costimulatory receptor ICOS and promoting expression of the transcriptional repressor BcI6.
引用
收藏
页码:980 / 990
页数:11
相关论文
共 47 条
[31]   Single Naive CD4+ T Cells from a Diverse Repertoire Produce Different Effector Cell Types during Infection [J].
Tubo, Noah J. ;
Pagan, Antonio J. ;
Taylor, Justin J. ;
Nelson, Ryan W. ;
Linehan, Jonathan L. ;
Ertelt, James M. ;
Huseby, Eric S. ;
Way, Sing Sing ;
Jenkins, Marc K. .
CELL, 2013, 153 (04) :785-796
[32]   Direct repression of prdm1 by Bcl-6 inhibits plasmacytic differentiation [J].
Tunyaplin, C ;
Shaffer, AL ;
Angelin-Duclos, CD ;
Yu, X ;
Staudt, LM ;
Calame, KL .
JOURNAL OF IMMUNOLOGY, 2004, 173 (02) :1158-1165
[33]   Pathophysiology of T follicular helper cells in humans and mice [J].
Ueno, Hideki ;
Banchereau, Jacques ;
Vinuesa, Carola G. .
NATURE IMMUNOLOGY, 2015, 16 (02) :142-152
[34]   A ThPOK-LRF transcriptional node maintains the integrity and effector potential of post-thymic CD4+ T cells [J].
Vacchio, Melanie S. ;
Wang, Lie ;
Bouladoux, Nicolas ;
Carpenter, Andrea C. ;
Xiong, Yumei ;
Wohlfert, Elizabeth ;
Song, Ki-Duk ;
Belkaid, Yasmine ;
Love, Paul E. ;
Bosselut, Remy .
NATURE IMMUNOLOGY, 2014, 15 (10) :947-U192
[35]   Canonical Wnt Signaling Negatively Modulates Regulatory T Cell Function [J].
van Loosdregt, Jorg ;
Fleskens, Veerle ;
Tiemessen, Machteld M. ;
Mokry, Michal ;
van Boxtel, Ruben ;
Meerding, Jenny ;
Pals, Cornelieke E. G. M. ;
Kurek, Dorota ;
Baert, Miranda R. M. ;
Delemarre, Eveline M. ;
Groene, Andrea ;
Koerkamp, Marianne J. A. Groot ;
Sijts, Alice J. A. M. ;
Nieuwenhuis, Edward E. S. ;
Maurice, Madelon M. ;
van Es, Johan H. ;
ten Berge, Derk ;
Holstege, Frank C. ;
Staal, Frank J. T. ;
Zaiss, Dietmar M. W. ;
Prakken, Berent J. ;
Coffer, Paul J. .
IMMUNITY, 2013, 39 (02) :298-310
[36]   Germinal Centers [J].
Victora, Gabriel D. ;
Nussenzweig, Michel C. .
ANNUAL REVIEW OF IMMUNOLOGY, VOL 30, 2012, 30 :429-457
[37]   Roquin Paralogs 1 and 2 Redundantly Repress the Icos and Ox40 Costimulator mRNAs and Control Follicular Helper T Cell Differentiation [J].
Vogel, Katharina U. ;
Edelmann, Stephanie L. ;
Jeltsch, Katharina M. ;
Bertossi, Arianna ;
Heger, Klaus ;
Heinz, Gitta A. ;
Zoeller, Jessica ;
Warth, Sebastian C. ;
Hoefig, Kai P. ;
Lohs, Claudia ;
Neff, Frauke ;
Kremmer, Elisabeth ;
Schick, Joel ;
Repsilber, Dirk ;
Geerlof, Arie ;
Blum, Helmut ;
Wurst, Wolfgang ;
Heikenwaelder, Mathias ;
Schmidt-Supprian, Marc ;
Heissmeyer, Vigo .
IMMUNITY, 2013, 38 (04) :655-668
[38]   A critical role for TCF-1 in T-lineage specification and differentiation [J].
Weber, Brittany Nicole ;
Chi, Anthony Wei-Shine ;
Chavez, Alejandro ;
Yashiro-Ohtani, Yumi ;
Yang, Qi ;
Shestova, Olga ;
Bhandoola, Avinash .
NATURE, 2011, 476 (7358) :63-+
[39]   ICOS maintains the T follicular helper cell phenotype by down-regulating Kruppel-like factor 2 [J].
Weber, Jan P. ;
Fuhrmann, Franziska ;
Feist, Randi K. ;
Lahmann, Annette ;
Al Baz, Maysun S. ;
Gentz, Lea-Jean ;
Van, Dana Vu ;
Mages, Hans W. ;
Haftmann, Claudia ;
Riedel, Rene ;
Gruen, Joachim R. ;
Schuh, Wolfgang ;
Kroczek, Richard A. ;
Radbruch, Andreas ;
Mashreghi, Mir-Farzin ;
Hutloff, Andreas .
JOURNAL OF EXPERIMENTAL MEDICINE, 2015, 212 (02) :217-233
[40]   Follicular T-helper cell recruitment governed by bystander B cells and ICOS-driven motility [J].
Xu, Heping ;
Li, Xuanying ;
Liu, Dan ;
Li, Jianfu ;
Zhang, Xu ;
Chen, Xin ;
Hou, Shiyue ;
Peng, Lixia ;
Xu, Chenguang ;
Liu, Wanli ;
Zhang, Lianfeng ;
Qi, Hai .
NATURE, 2013, 496 (7446) :523-+