Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells.
CD4⁺ T cell differentiation is regulated by specialized antigen-presenting cells. Dendritic cells (DCs) produce cytokines that promote naive CD4⁺ T cell differentiation into T helper 1 (Th1), Th17, and inducible T regulatory (iTreg) cells. However, the initiation of Th2 cell responses remains poorly understood, although it is likely that more than one mechanism might be involved. Here we have defined a specific DC subset that is involved in Th2 cell differentiation in vivo in response to a protease allergen, as well as infection with Nippostrongylus brasiliensis. We have demonstrated that this subset is controlled by the transcription factor interferon regulatory factor 4 (IRF4), which is required for their differentiation and Th2 cell-inducing function. IRF4 is known to control Th2 cell differentiation and Th2 cell-associated suppressing function in Treg cells. Our finding suggests that IRF4 also plays a role in DCs where it controls the initiation of Th2 cell responses.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
Yan
Y
Gao
Simone A
SA
Nish
Ruoyi
R
Jiang
Lin
L
Hou
Paula
P
Licona-Limón
Jason S
JS
Weinstein
Hongyu
H
Zhao
Ruslan
R
Medzhitov
D000485:Allergens / Q000276:immunology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D002454:Cell Differentiation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D005786:Gene Expression Regulation; D007111:Immunity, Cellular; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009559:Nippostrongylus / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D015398:Signal Transduction; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D000099218:Interferon Regulatory Factor-4
D000485:Allergens; D050835:Interferon Regulatory Factors; D010047:Ovalbumin; D000099218:Interferon Regulatory Factor-4