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PMID: 23334789 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Mutual expression of the transcription factors Runx3 and ThPOK regulates intestinal CD4⁺ T cell immunity.

Nature immunology ·Vol. 14 ·No. 3 ·2013-03-00 ·Pages 271-80

Reis BS, Rogoz A, Costa-Pinto FA, Taniuchi I, Mucida D

Abstract

The gut mucosa hosts large numbers of activated lymphocytes that are exposed to stimuli from the diet, microbiota and pathogens. Although CD4(+) T cells are crucial for defense, intestinal homeostasis precludes exaggerated responses to luminal contents, whether they are harmful or not. We investigated mechanisms used by CD4(+) T cells to avoid excessive activation in the intestine. Using genetic tools to label and interfere with T cell-development transcription factors, we found that CD4(+) T cells acquired the CD8-lineage transcription factor Runx3 and lost the CD4-lineage transcription factor ThPOK and their differentiation into the T(H)17 subset of helper T cells and colitogenic potential, in a manner dependent on transforming growth factor-β (TGF-β) and retinoic acid. Our results demonstrate considerable plasticity in the CD4(+) T cell lineage that allows chronic exposure to luminal antigens without pathological inflammation.

MeSH Terms
Animals CD4-Positive T-Lymphocytes/immunology,metabolism CD8 Antigens/immunology Cell Differentiation Cells, Cultured Citrobacter rodentium/immunology Colitis Core Binding Factor Alpha 3 Subunit/metabolism Enterobacteriaceae Infections/immunology Homeodomain Proteins/genetics Inflammation/immunology Intestinal Mucosa/immunology Intestines/immunology Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Knockout Signal Transduction Tamoxifen/pharmacology Transcription Factors/metabolism Transforming Growth Factor beta/metabolism Tretinoin/metabolism
Chemicals
CD8 Antigens Core Binding Factor Alpha 3 Subunit Homeodomain Proteins Runx3 protein, mouse Th-POK protein, mouse Transcription Factors Transforming Growth Factor beta Tamoxifen RAG-1 protein Tretinoin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Reis Bernardo Sgarbi
Laboratory of Mucosal Immunology, The Rockefeller University, New York, New York, USA.
Rogoz Aneta
Costa-Pinto Frederico Azevedo
Taniuchi Ichiro
Mucida Daniel
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.2518
Published
2013-03-00
Epub
2013-00-20
Pages
271-80
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC3804366
Subset
IM
Grants
NIDDK NIH HHS · R01 DK093674 · United States
NIDDK NIH HHS · R01 DK093674-01 · United States
Corrections
CommentIn
PMID: 23370307
External Links
PubMed source DOI: 10.1038/ni.2518 PMC Full Text View journal details
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