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PMID: 21074460 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

T regulatory cells maintain intestinal homeostasis by suppressing γδ T cells.

Immunity ·Vol. 33 ·No. 5 ·2010-11-24 ·Pages 791-803

Park SG, Mathur R, Long M, Hosh N, Hao L, Hayden MS, Ghosh S

Abstract

Immune tolerance against enteric commensal bacteria is important for preventing intestinal inflammation. Deletion of phosphoinositide-dependent protein kinase 1 (Pdk1) in T cells via Cd4-Cre induced chronic inflammation of the intestine despite the importance of PDK1 in T cell activation. Analysis of colonic intraepithelial lymphocytes of PDK1-deficient mice revealed markedly increased CD8α(+) T cell receptor (TCR)γδ(+) T cells, including an interleukin-17 (IL-17)-expressing population. TCRγδ(+) T cells were responsible for the inflammatory colitis as shown by the fact that deletion of Tcrd abolished spontaneous colitis in the PDK1-deficient mice. This dysregulation of intestinal TCRγδ(+) T cells was attributable to a reduction in the number and functional capacity of PDK1-deficient T regulatory (Treg) cells. Adoptive transfer of wild-type Treg cells abrogated the spontaneous activation and proliferation of intestinal TCRγδ(+) T cells observed in PDK1-deficient mice and prevented the development of colitis. Therefore, suppression of intestinal TCRγδ(+) T cells by Treg cells maintains enteric immune tolerance.

MeSH Terms
Adoptive Transfer Animals CD8 Antigens/immunology Colitis/enzymology,etiology,immunology Homeostasis/immunology Immune Tolerance Interleukin-17/immunology Intestines/enzymology,immunology Lymphocyte Activation/immunology Mice Protein Serine-Threonine Kinases/genetics Pyruvate Dehydrogenase Acetyl-Transferring Kinase Receptors, Antigen, T-Cell, gamma-delta/immunology T-Lymphocyte Subsets/enzymology,immunology T-Lymphocytes, Regulatory/enzymology,immunology
Chemicals
CD8 Antigens CD8 antigen, alpha chain Interleukin-17 Pdk1 protein, mouse Pyruvate Dehydrogenase Acetyl-Transferring Kinase Receptors, Antigen, T-Cell, gamma-delta Protein Serine-Threonine Kinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Park Sung-Gyoo
Department of Microbiology & Immunology, Columbia University, College of Physicians & Surgeons, New York, NY 10032, USA.
Mathur Ramkumar
Long Meixiao
Hosh Namiko
Hao Liming
Hayden Matthew S
Ghosh Sankar
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2010.10.014
Published
2010-11-24
Epub
2010-00-11
Pages
791-803
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2996054
Subset
IM
Grants
NIAID NIH HHS · R01-AI59440 · United States
NIAID NIH HHS · R01 AI068977-04 · United States
NIAID NIH HHS · R01 AI068977-02 · United States
NIAID NIH HHS · R01 AI068977-01 · United States
NIAID NIH HHS · R01 AI068977 · United States
NIAID NIH HHS · R01 AI068977-06 · United States
NIAID NIH HHS · R01 AI068977-03 · United States
NIAID NIH HHS · R01 AI059440 · United States
NIAID NIH HHS · R01 AI068977-05 · United States
Corrections
CommentIn
PMID: 21218660
External Links
PubMed source DOI: 10.1016/j.immuni.2010.10.014 PMC Full Text View journal details
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