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

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ICOS maintains the T follicular helper cell phenotype by down-regulating Krüppel-like factor 2. / Weber, Jan P; Fuhrmann, Franziska; Feist, Randi K; Lahmann, Annette; Al Baz, Maysun S; Gentz, Lea-Jean; Vu Van, Dana; Mages, Hans W; Haftmann, Claudia; Riedel, René; Grün, Joachim R; Schuh, Wolfgang; Kroczek, Richard A; Radbruch, Andreas; Mashreghi, Mir-Farzin; Hutloff, Andreas.

In: J EXP MED, Vol. 212, No. 2, 09.02.2015, p. 217-33.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Weber, JP, Fuhrmann, F, Feist, RK, Lahmann, A, Al Baz, MS, Gentz, L-J, Vu Van, D, Mages, HW, Haftmann, C, Riedel, R, Grün, JR, Schuh, W, Kroczek, RA, Radbruch, A, Mashreghi, M-F & Hutloff, A 2015, 'ICOS maintains the T follicular helper cell phenotype by down-regulating Krüppel-like factor 2', J EXP MED, vol. 212, no. 2, pp. 217-33. https://doi.org/10.1084/jem.20141432

APA

Weber, J. P., Fuhrmann, F., Feist, R. K., Lahmann, A., Al Baz, M. S., Gentz, L-J., Vu Van, D., Mages, H. W., Haftmann, C., Riedel, R., Grün, J. R., Schuh, W., Kroczek, R. A., Radbruch, A., Mashreghi, M-F., & Hutloff, A. (2015). ICOS maintains the T follicular helper cell phenotype by down-regulating Krüppel-like factor 2. J EXP MED, 212(2), 217-33. https://doi.org/10.1084/jem.20141432

Vancouver

Weber JP, Fuhrmann F, Feist RK, Lahmann A, Al Baz MS, Gentz L-J et al. ICOS maintains the T follicular helper cell phenotype by down-regulating Krüppel-like factor 2. J EXP MED. 2015 Feb 9;212(2):217-33. https://doi.org/10.1084/jem.20141432

Bibtex

@article{f8bc7d5a687f4ffe91fc3358cf2a9794,
title = "ICOS maintains the T follicular helper cell phenotype by down-regulating Kr{\"u}ppel-like factor 2",
abstract = "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. ",
keywords = "Animals, CD28 Antigens/metabolism, Cell Differentiation/genetics, Down-Regulation, Female, Forkhead Box Protein O1, Forkhead Transcription Factors/metabolism, Gene Expression, Gene Expression Regulation, Germinal Center/immunology, Humans, Inducible T-Cell Co-Stimulator Ligand/metabolism, Inducible T-Cell Co-Stimulator Protein/metabolism, Kruppel-Like Transcription Factors/genetics, Membrane Glycoproteins/metabolism, Mice, Mice, Knockout, Palatine Tonsil/immunology, Phenotype, Protein Binding, Receptors, CCR7/metabolism, Receptors, CXCR5/metabolism, Signal Transduction, T-Lymphocyte Subsets, T-Lymphocytes, Helper-Inducer/cytology",
author = "Weber, {Jan P} and Franziska Fuhrmann and Feist, {Randi K} and Annette Lahmann and {Al Baz}, {Maysun S} and Lea-Jean Gentz and {Vu Van}, Dana and Mages, {Hans W} and Claudia Haftmann and Ren{\'e} Riedel and Gr{\"u}n, {Joachim R} and Wolfgang Schuh and Kroczek, {Richard A} and Andreas Radbruch and Mir-Farzin Mashreghi and Andreas Hutloff",
note = "{\textcopyright} 2015 Weber et al.",
year = "2015",
month = feb,
day = "9",
doi = "10.1084/jem.20141432",
language = "English",
volume = "212",
pages = "217--33",
journal = "J EXP MED",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "2",

}

RIS

TY - JOUR

T1 - ICOS maintains the T follicular helper cell phenotype by down-regulating Krüppel-like factor 2

AU - Weber, Jan P

AU - Fuhrmann, Franziska

AU - Feist, Randi K

AU - Lahmann, Annette

AU - Al Baz, Maysun S

AU - Gentz, Lea-Jean

AU - Vu Van, Dana

AU - Mages, Hans W

AU - Haftmann, Claudia

AU - Riedel, René

AU - Grün, Joachim R

AU - Schuh, Wolfgang

AU - Kroczek, Richard A

AU - Radbruch, Andreas

AU - Mashreghi, Mir-Farzin

AU - Hutloff, Andreas

N1 - © 2015 Weber et al.

PY - 2015/2/9

Y1 - 2015/2/9

N2 - 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.

AB - 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.

KW - Animals

KW - CD28 Antigens/metabolism

KW - Cell Differentiation/genetics

KW - Down-Regulation

KW - Female

KW - Forkhead Box Protein O1

KW - Forkhead Transcription Factors/metabolism

KW - Gene Expression

KW - Gene Expression Regulation

KW - Germinal Center/immunology

KW - Humans

KW - Inducible T-Cell Co-Stimulator Ligand/metabolism

KW - Inducible T-Cell Co-Stimulator Protein/metabolism

KW - Kruppel-Like Transcription Factors/genetics

KW - Membrane Glycoproteins/metabolism

KW - Mice

KW - Mice, Knockout

KW - Palatine Tonsil/immunology

KW - Phenotype

KW - Protein Binding

KW - Receptors, CCR7/metabolism

KW - Receptors, CXCR5/metabolism

KW - Signal Transduction

KW - T-Lymphocyte Subsets

KW - T-Lymphocytes, Helper-Inducer/cytology

U2 - 10.1084/jem.20141432

DO - 10.1084/jem.20141432

M3 - SCORING: Journal article

C2 - 25646266

VL - 212

SP - 217

EP - 233

JO - J EXP MED

JF - J EXP MED

SN - 0022-1007

IS - 2

ER -