ICOS maintains the T follicular helper cell phenotype by down-regulating Kruppel-like factor 2

被引：223

作者：

Weber, Jan P. ^{[1
,2
]}

Fuhrmann, Franziska ^{[1
,2
]}

Feist, Randi K. ^{[1
,2
]}

Lahmann, Annette ^{[1
,2
]}

Al Baz, Maysun S. ^{[1
,2
]}

Gentz, Lea-Jean ^{[1
,2
]}

Van, Dana Vu ^{[1
,2
]}

Mages, Hans W. ^{[2
]}

Haftmann, Claudia ^{[1
]}

Riedel, Rene ^{[1
]}

Gruen, Joachim R. ^{[1
]}

Schuh, Wolfgang ^{[3
]}

Kroczek, Richard A. ^{[2
]}

Radbruch, Andreas ^{[1
]}

Mashreghi, Mir-Farzin ^{[1
]}

Hutloff, Andreas ^{[1
,2
]}

机构：

[1] German Rheumatism Res Ctr, D-10117 Berlin, Germany

[2] Robert Koch Inst, D-13353 Berlin, Germany

[3] Univ Erlangen Nurnberg, Div Mol Immunol, D-91054 Erlangen, Germany

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2015年 / 212卷 / 02期

基金：

欧洲研究理事会;

关键词：

B-CELLS; INDUCIBLE COSTIMULATOR; TRANSCRIPTION FACTOR; L-SELECTIN; TH2; DIFFERENTIATION; IN-VIVO; RECEPTOR; LIGAND; EXPRESSION; GENERATION;

D O I：

10.1084/jem.20141432

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The co-stimulators ICOS (inducible T cell co-stimulator) and CD28 are both important for T follicular helper (TFH) cells, yet their individual contributions are unclear. Here, we show that each molecule plays an exclusive role at different stages of TFH cell development. While CD28 regulated early expression of the master transcription factor Bcl-6, ICOS co-stimulation was essential to maintain the phenotype by regulating the novel TFH transcription factor Klf2 via Foxo1. Klf2 directly binds to Cxcr5, Ccr7, Psgl-1, and S1pr1, and low levels of Klf2 were essential to maintain this typical TFH homing receptor pattern. Blocking ICOS resulted in relocation of fully developed TFH cells back to the T cell zone and reversion of their phenotype to non-TFH effector cells, which ultimately resulted in breakdown of the germinal center response. Our study describes for the first time the exclusive role of ICOS and its downstream signaling in the maintenance of TFH cells by controlling their anatomical localization in the B cell follicle.

引用

页码：217 / 233

页数：17

共 61 条

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