Control of T Helper 2 Responses by Transcription Factor IRF4-Dependent Dendritic Cells

Abstract

SUMMARY 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.

IL-4–Producing Dendritic Cells Induced during Schistosoma japonica Infection Promote Th2 Cells via IL-4–Dependent Pathway

“…Non monocyte-derived resident CD301b-positive dermal DCs are critical in initiation of Th2 cell responses in alum-and papain-induced Th2 response when Ags are given locally (34). A unique IRF-4-dependent DC subset is induced under GM-CSF treatment, which can specifically promote Th2 response (35). In this study, we found that infection by S. japonica promote the formation of specialized DC2 subset from bone marrow precursor cells, likely through egg Ags, which facilitate Th2 polarization.…”

Murine germinal center B cells require functional Fms-like tyrosine kinase 3 signaling for IgG1 class-switch recombination

“…DCs are important for T-cell activation and differentiation and subsequent IgG CSR (44,45). FLKO mice have a significantly reduced number of DCs, and previous studies on the role for FL in mediating DC-and T-cell-dependent production of IgG have rendered contradictory results (16,46).…”

Vitamin D immunoregulation through dendritic cells

“…In such systems, CD11c +  MHCII + progeny (fulfilling classical DC definitions) comprise a significant portion of MHCII intermediate cells having a phenotypic, developmental and transcriptional profile reminiscent of macrophages (‘GM‐Mac’). The MHC‐II high ‘GM‐DC’ are indeed bona fide DC, depend on interferon regulatory factor 4, are probably derived from pre‐cDC and efficiently present antigen to CD4 T cells 44, 45, 46. Using this differentiation protocol, a framework similar to that for human moDC was developed where murine DC are rendered tolerogenic by 1,25‐OH‐VD3 during differentiation.…”