title: Mutual expression of the transcription factors Runx3 and ThPOK regulates intestinal CD4⁺ T cell immunity.
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.
authors: Laboratory of Mucosal Immunology, The Rockefeller University, New York, New York, USA.
authors: Bernardo Sgarbi
authors: BS
authors: Reis
authors: Aneta
authors: A
authors: Rogoz
authors: Frederico Azevedo
authors: FA
authors: Costa-Pinto
authors: Ichiro
authors: I
authors: Taniuchi
authors: Daniel
authors: D
authors: Mucida
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D016827:CD8 Antigens / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D044082:Citrobacter rodentium / Q000276:immunology; D003092:Colitis; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism*; D004756:Enterobacteriaceae Infections / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D007249:Inflammation / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D007422:Intestines / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D013629:Tamoxifen / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; D050677:Core Binding Factor Alpha 3 Subunit; D018398:Homeodomain Proteins; D013629:Tamoxifen; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014212:Tretinoin; C493730:Runx3 protein, mouse; C497211:Zbtb7b protein, mouse; C064658:RAG-1 protein