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PMID: 19098919 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells.

Nature immunology ·Vol. 10 ·No. 2 ·2009-02-00 ·Pages 167-75

Bauquet AT, Jin H, Paterson AM, Mitsdoerffer M, Ho IC, Sharpe AH, Kuchroo VK

Abstract

The inducible costimulatory molecule ICOS has been suggested to be important in the development of interleukin 17 (IL-17)-producing helper T cells (T(H)-17 cells) and of follicular helper T cells (T(FH) cells). Here we show that ICOS-deficient mice had no defect in T(H)-17 differentiation but had fewer T(H)-17 cells after IL-23 stimulation and fewer T(FH) cells. We also show that T(FH) cells produced IL-17 and that T(FH) cells in ICOS-deficient mice were defective in IL-17 production. Both T(H)-17 and T(FH) cells had higher expression of the transcription factor c-Maf. Genetic loss of c-Maf resulted in a defect in IL-21 production and fewer T(H)-17 and T(FH) cells. Thus our data suggest that ICOS-induced c-Maf regulates IL-21 production that in turn regulates the expansion of T(H)-17 and T(FH) cells.

MeSH Terms
Animals Antigens, Differentiation, T-Lymphocyte/genetics,immunology,metabolism Cell Differentiation/immunology Cell Proliferation Encephalomyelitis, Autoimmune, Experimental/immunology Enzyme-Linked Immunosorbent Assay Flow Cytometry Gene Expression Regulation/immunology Inducible T-Cell Co-Stimulator Protein Interleukin-17/immunology,metabolism Interleukins/biosynthesis,immunology Mice Mice, Transgenic Oligonucleotide Array Sequence Analysis Proto-Oncogene Proteins c-maf/biosynthesis,immunology Reverse Transcriptase Polymerase Chain Reaction T-Lymphocyte Subsets/cytology,immunology,metabolism T-Lymphocytes, Helper-Inducer/cytology,immunology,metabolism
Chemicals
Antigens, Differentiation, T-Lymphocyte Icos protein, mouse Inducible T-Cell Co-Stimulator Protein Interleukin-17 Interleukins Maf protein, mouse Proto-Oncogene Proteins c-maf interleukin-21
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Bauquet Aurelie T
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Jin Hulin
Paterson Alison M
Mitsdoerffer Meike
Ho I-Cheng
Sharpe Arlene H
Kuchroo Vijay K
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1690
Published
2009-02-00
Epub
2008-00-21
Pages
167-75
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2742982
Subset
IM
Grants
NINDS NIH HHS · P01NS38037-04 · United States
NINDS NIH HHS · 2R01NS35685-06 · United States
NIAID NIH HHS · P01 AI056299 · United States
NIAID NIH HHS · 1P01AI56299 · United States
NINDS NIH HHS · R01 NS045937 · United States
NIAID NIH HHS · R37 AI38310 · United States
NINDS NIH HHS · R37 NS030843-11 · United States
NINDS NIH HHS · R01 NS035685 · United States
NINDS NIH HHS · R01 NS046414-01 · United States
NIAID NIH HHS · P01 AI056299-01 · United States
NIAID NIH HHS · R01 AI044880-03 · United States
NINDS NIH HHS · P01 NS038037-040001 · United States
NINDS NIH HHS · R01 NS035685-06 · United States
NIAID NIH HHS · R37 AI038310 · United States
NIAID NIH HHS · 1R01AI44880-03 · United States
NIAID NIH HHS · R01 AI044880 · United States
NIAID NIH HHS · P01 AI039671 · United States
NINDS NIH HHS · R37 NS030843 · United States
NIAID NIH HHS · R37 AI038310-12 · United States
PHS HHS · 2P01A139671-07 · United States
NINDS NIH HHS · R01 NS045937-01 · United States
NINDS NIH HHS · 2R37NS30843-11 · United States
NINDS NIH HHS · 1R01NS045937-01 · United States
NINDS NIH HHS · R01 NS046414 · United States
NIAID NIH HHS · P01 AI039671-070005 · United States
NINDS NIH HHS · 1R01NS046414 · United States
NINDS NIH HHS · P01 NS038037 · United States
Corrections
CommentIn
PMID: 19148197
External Links
PubMed source DOI: 10.1038/ni.1690 PMC Full Text View journal details
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