Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions

Yeonseok Chung; Shinya Tanaka; Fuliang Chu; Roza I. Nurieva; Gustavo J. Martinez; Seema Rawal; Yi Hong Wang; Hoyong Lim; Joseph M. Reynolds; Xiao Hui Zhou; Hui Min Fan; Zhong Ming Liu; Sattva S. Neelapu; Chen Dong

doi:10.1038/nm.2426

Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions

Yeonseok Chung, Shinya Tanaka, Fuliang Chu, Roza I. Nurieva, Gustavo J. Martinez, Seema Rawal, Yi Hong Wang, Hoyong Lim, Joseph M. Reynolds, Xiao Hui Zhou, Hui Min Fan, Zhong Ming Liu, Sattva S. Neelapu, Chen Dong

Research output: Contribution to journal › Article › peer-review

824 Citations (Scopus)

Abstract

Foxp3⁺ regulatory T (T_reg) cells suppress different types of immune responses to help maintain homeostasis in the body. How T reg cells regulate humoral immunity, including germinal center reactions, is unclear. Here we identify a subset of T reg cells expressing CXCR5 and Bcl-6 that localize to the germinal centers in mice and humans. The expression of CXCR5 on T reg cells depends on Bcl-6. These CXCR5 + Bcl-6 + T reg cells are absent in the thymus but can be generated de novo from CXCR5-Foxp3⁺ natural T reg precursors. A lack of CXCR5 + T reg cells leads to greater germinal center reactions including germinal center B cells, affinity maturation of antibodies and the differentiation of plasma cells. These results unveil a Bcl-6-CXCR5 axis in T reg cells that drives the development of follicular regulatory T (T_FR) cells that function to inhibit the germinal center reactions.

Original language	English
Pages (from-to)	983-988
Number of pages	6
Journal	Nature medicine
Volume	17
Issue number	8
DOIs	https://doi.org/10.1038/nm.2426
Publication status	Published - Aug 2011
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)

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10.1038/nm.2426

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@article{3d583f0a1ecf489c8c7bde872f67b52e,

title = "Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions",

abstract = "Foxp3+ regulatory T (Treg) cells suppress different types of immune responses to help maintain homeostasis in the body. How T reg cells regulate humoral immunity, including germinal center reactions, is unclear. Here we identify a subset of T reg cells expressing CXCR5 and Bcl-6 that localize to the germinal centers in mice and humans. The expression of CXCR5 on T reg cells depends on Bcl-6. These CXCR5 + Bcl-6 + T reg cells are absent in the thymus but can be generated de novo from CXCR5-Foxp3+ natural T reg precursors. A lack of CXCR5 + T reg cells leads to greater germinal center reactions including germinal center B cells, affinity maturation of antibodies and the differentiation of plasma cells. These results unveil a Bcl-6-CXCR5 axis in T reg cells that drives the development of follicular regulatory T (TFR) cells that function to inhibit the germinal center reactions.",

author = "Yeonseok Chung and Shinya Tanaka and Fuliang Chu and Nurieva, {Roza I.} and Martinez, {Gustavo J.} and Seema Rawal and Wang, {Yi Hong} and Hoyong Lim and Reynolds, {Joseph M.} and Zhou, {Xiao Hui} and Fan, {Hui Min} and Liu, {Zhong Ming} and Neelapu, {Sattva S.} and Chen Dong",

note = "Funding Information: We thank R. Dalla-Favera (Columbia University) for the Bcl-6-deficient mice, A. Rudensky (Memorial Sloan-Kettering Cancer Center) for Foxp3GFP reporter mice, D. Tran (University of Texas at Houston) for the antibody to Helios, Z. He, K. Ramirez and K. Dwyer for help with cell sorting and the entire Dong lab for their help. This work was supported by research grants from the US National Institutes of Health (C.D., to R.I.N. and to S.S.N.), the Leukemia and Lymphoma Society (C.D.), the MD Anderson Cancer Center (C.D.), the American Heart Association (Y.C.), Doris Duke Charitable Foundation Clinical Scientist Development Award (S.S.N.) and China Ministry of Science and Technology Protein Science Key Research Project (X.Z., H.F. and C.D.).",

year = "2011",

month = aug,

doi = "10.1038/nm.2426",

language = "English",

volume = "17",

pages = "983--988",

journal = "Nature medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

number = "8",

}

TY - JOUR

T1 - Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions

AU - Chung, Yeonseok

AU - Tanaka, Shinya

AU - Chu, Fuliang

AU - Nurieva, Roza I.

AU - Martinez, Gustavo J.

AU - Rawal, Seema

AU - Wang, Yi Hong

AU - Lim, Hoyong

AU - Reynolds, Joseph M.

AU - Zhou, Xiao Hui

AU - Fan, Hui Min

AU - Liu, Zhong Ming

AU - Neelapu, Sattva S.

AU - Dong, Chen

N1 - Funding Information: We thank R. Dalla-Favera (Columbia University) for the Bcl-6-deficient mice, A. Rudensky (Memorial Sloan-Kettering Cancer Center) for Foxp3GFP reporter mice, D. Tran (University of Texas at Houston) for the antibody to Helios, Z. He, K. Ramirez and K. Dwyer for help with cell sorting and the entire Dong lab for their help. This work was supported by research grants from the US National Institutes of Health (C.D., to R.I.N. and to S.S.N.), the Leukemia and Lymphoma Society (C.D.), the MD Anderson Cancer Center (C.D.), the American Heart Association (Y.C.), Doris Duke Charitable Foundation Clinical Scientist Development Award (S.S.N.) and China Ministry of Science and Technology Protein Science Key Research Project (X.Z., H.F. and C.D.).

PY - 2011/8

Y1 - 2011/8

N2 - Foxp3+ regulatory T (Treg) cells suppress different types of immune responses to help maintain homeostasis in the body. How T reg cells regulate humoral immunity, including germinal center reactions, is unclear. Here we identify a subset of T reg cells expressing CXCR5 and Bcl-6 that localize to the germinal centers in mice and humans. The expression of CXCR5 on T reg cells depends on Bcl-6. These CXCR5 + Bcl-6 + T reg cells are absent in the thymus but can be generated de novo from CXCR5-Foxp3+ natural T reg precursors. A lack of CXCR5 + T reg cells leads to greater germinal center reactions including germinal center B cells, affinity maturation of antibodies and the differentiation of plasma cells. These results unveil a Bcl-6-CXCR5 axis in T reg cells that drives the development of follicular regulatory T (TFR) cells that function to inhibit the germinal center reactions.

AB - Foxp3+ regulatory T (Treg) cells suppress different types of immune responses to help maintain homeostasis in the body. How T reg cells regulate humoral immunity, including germinal center reactions, is unclear. Here we identify a subset of T reg cells expressing CXCR5 and Bcl-6 that localize to the germinal centers in mice and humans. The expression of CXCR5 on T reg cells depends on Bcl-6. These CXCR5 + Bcl-6 + T reg cells are absent in the thymus but can be generated de novo from CXCR5-Foxp3+ natural T reg precursors. A lack of CXCR5 + T reg cells leads to greater germinal center reactions including germinal center B cells, affinity maturation of antibodies and the differentiation of plasma cells. These results unveil a Bcl-6-CXCR5 axis in T reg cells that drives the development of follicular regulatory T (TFR) cells that function to inhibit the germinal center reactions.

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U2 - 10.1038/nm.2426

DO - 10.1038/nm.2426

M3 - Article

C2 - 21785430

AN - SCOPUS:79961158055

SN - 1078-8956

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SP - 983

EP - 988

JO - Nature medicine

JF - Nature medicine

IS - 8

ER -

Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions

Abstract

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