Notch Signaling Regulates Follicular Helper T Cell Differentiation

被引：61

作者：

Auderset, Floriane ^{[1
,2
]}

Schuster, Steffen ^{[1
,2
]}

Fasnacht, Nicolas ^{[3
]}

Coutaz, Manuel ^{[1
,2
]}

Charmoy, Melanie ^{[1
,2
]}

Koch, Ute ^{[3
]}

Favre, Stephanie ^{[1
]}

Wilson, Anne ^{[4
]}

Trottein, Francois ^{[5
]}

Alexander, James ^{[6
]}

Luther, Sanjiv A. ^{[1
]}

MacDonald, H. Robson ^{[4
]}

Radtke, Freddy ^{[3
]}

Tacchini-Cottier, Fabienne ^{[1
,2
]}

机构：

[1] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

[2] Univ Lausanne, World Hlth Org Immunol Res & Training Ctr, CH-1066 Epalinges, Switzerland

[3] Ecole Polytech Fed Lausanne, Inst Suisse Rech Expt Canc, CH-1015 Lausanne, Switzerland

[4] Univ Lausanne, Ludwig Ctr Canc Res, CH-1066 Epalinges, Switzerland

[5] Univ Lille Nord France, Ctr Infect & Immun Lille, Inst Pasteur Lille, CNRS,Unite Mixte Rech 8204,INSERM,U1019, F-59019 Lille, France

[6] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow G4 0RE, Lanark, Scotland

来源：

JOURNAL OF IMMUNOLOGY | 2013年 / 191卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

LINEAGE COMMITMENT; GATA3; EXPRESSION; B-CELLS; INFECTION; IMMUNITY; IL-21; MAINTENANCE; T-HELPER-2; RESPONSES; BLIMP-1;

D O I：

10.4049/jimmunol.1300643

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 specialized in providing help for B cell differentiation and Ab secretion. Several positive and negative regulators of TFH cell differentiation have been described but their control is not fully understood. In this study, we show that Notch signaling in T cells is a major player in the development and function of TFH cells. T cell-specific gene ablation of Notch1 and Notch2 impaired differentiation of TFH cells in draining lymph nodes of mice immunized with T-dependent Ags or infected with parasites. Impaired TFH cell differentiation correlated with deficient germinal center development and the absence of high-affinity Abs. The impact of loss of Notch on TFH cell differentiation was largely independent of its effect on IL-4. These results show a previously unknown role for Notch in the regulation of TFH cell differentiation and function with implications for the control of this T cell population.

引用

页码：2344 / 2350

页数：7

共 37 条

[31] The interleukin-4 enhancer CNS-2 is regulated by Notch signals and controls initial expression in NKT cells and memory-type CD4 T cells [J].

Tanaka, Shinya ;

Tsukada, Jun ;

Suzuki, Wataru ;

Hayashi, Katsuhiko ;

Tanigaki, Kenji ;

Tsuji, Masayuki ;

Inoue, Hiromasa ;

Honjo, Tasuku ;

Kubo, Masato .

IMMUNITY, 2006, 24 (06) :689-701

[32] Regulation of αβ/γδ, T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling [J].

Tanigaki, K ;

Tsuji, M ;

Yamamoto, N ;

Han, H ;

Tsukada, J ;

Inoue, H ;

Kubo, M ;

Honjo, T .

IMMUNITY, 2004, 20 (05) :611-622

[33] Notch signaling is an important regulator of type 2 immunity [J].

Tu, LL ;

Fang, TC ;

Artis, D ;

Shestova, O ;

Pross, SE ;

Maillard, I ;

Pear, WS .

JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 202 (08) :1037-1042

[34] Interleukin-4 Production by Follicular Helper T Cells Requires the Conserved Il4 Enhancer Hypersensitivity Site V [J].

Vijayanand, Pandurangan ;

Seumois, Gregory ;

Simpson, Laura J. ;

Abdul-Wajid, Sarah ;

Baumjohann, Dirk ;

Panduro, Marisella ;

Huang, Xiaozhu ;

Interlandi, Jeneen ;

Djuretic, Vane M. ;

Brown, Daniel R. ;

Sharpe, Arlene H. ;

Rao, Anjana ;

Ansel, K. Mark .

IMMUNITY, 2012, 36 (02) :175-187

[35] The Transcriptional Repressor Bcl-6 Directs T Follicular Helper Cell Lineage Commitment [J].

Yu, Di ;

Rao, Sudha ;

Tsai, Louis M. ;

Lee, Sau K. ;

He, Yiqing ;

Sutcliffe, Elissa L. ;

Srivastava, Monika ;

Linterman, Michelle ;

Zheng, Lei ;

Simpson, Nicholas ;

Ellyard, Julia I. ;

Parish, Ian A. ;

Ma, Cindy S. ;

Li, Qi-Jing ;

Parish, Christopher R. ;

Mackay, Charles R. ;

Vinuesa, Carola G. .

IMMUNITY, 2009, 31 (03) :457-468

[36] Germinal Center T Follicular Helper Cell IL-4 Production Is Dependent on Signaling Lymphocytic Activation Molecule Receptor (CD150) [J].

Yusuf, Isharat ;

Kageyama, Robin ;

Monticelli, Laurel ;

Johnston, Robert J. ;

DiToro, Daniel ;

Hansen, Kyle ;

Barnett, Burton ;

Crotty, Shane .

JOURNAL OF IMMUNOLOGY, 2010, 185 (01) :190-202

[37] T follicular helper cells differentiate from Th2 cells in response to helminth antigens [J].

Zaretsky, Arielle Glatman ;

Taylor, Justin J. ;

King, Irah L. ;

Marshall, Fraser A. ;

Mohrs, Markus ;

Pearce, Edward J. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (05) :991-999

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