Klf4 Expression in Conventional Dendritic Cells Is Required for T Helper 2 Cell Responses

The two major lineages of classical dendritic cells (cDCs) express and require either IRF8 or IRF4 transcription factors for their development and function. IRF8-dependent cDCs promote anti-viral and T-helper 1 (Th1) cell responses, whereas IRF4-expressing cDCs have been implicated in controlling both Th2 and Th17 cell responses. Here, we have provided evidence that Kruppel-like factor 4 (Klf4) is required in IRF4-expressing cDCs to promote Th2, but not Th17, cell responses in vivo. Conditional Klf4 deletion within cDCs impaired Th2 cell responses during Schistosoma mansoni infection, Schistosoma egg antigen (SEA) immunization, and house dust mite (HDM) challenge without affecting cytotoxic T lymphocyte (CTL), Th1 cell, or Th17 cell responses to herpes simplex virus, Toxoplasma gondii, and Citrobacter rodentium infections. Further, Klf4 deletion reduced IRF4 expression in pre-cDCs and resulted in selective loss of IRF4-expressing cDCs subsets in several tissues. These results indicate that Klf4 guides a transcriptional program promoting IRF4-expressing cDCs heterogeneity. [Display omitted] •Klf4 is required for the development of a subset of IRF4-expressing cDCs•Klf4 deletion results in reduced pre-cDCs•A specific Klf4-dependent subset can be identified in several tissues•Klf4fl/flItgax-cre mice have selectively impaired Th2 cell immunity The IRF4-expressing cDCs subset is highly heterogeneous and has been implicated in priming Th17, as well as Th2 cell immunity. Murphy and colleagues dissect this heterogeneity showing a developmental requirement for Klf4 on specific subsets across several tissues. Moreover, Klf4 guides a transcriptional program necessary for Th2 cell immunity.