Blimp-1 is essential for Th2 cell development and allergic asthma

A Th2 immune response is central to allergic airway inflammation, which afflicts millions worldwide. However, the mechanisms that augment GATA3 expression in an antigen-primed developing Th2 cell are not well understood. Here, we describe an unexpected role for Blimp-1, a transcriptional repressor that constrains autoimmunity, as an upstream promoter of GATA3 expression that is critical for Th2 cell development in the lung, but dispensable for T FH function and IgE production. Mechanistically, Blimp-1 acts through Bcl6, which is necessary to drive GATA3 expression. Surprisingly, the anti-inflammatory cytokine IL-10, but not the pro-inflammatory cytokines IL-6 or IL-21, is required via STAT3 activation to upregulate Blimp-1 and promote Th2 cell development. These data reveal a hitherto unappreciated role for an IL-10-STAT3-Blimp-1 circuit as an initiator of an inflammatory Th2 response in the lung to allergens. Thus, Blimp-1 in a context-dependent fashion can drive inflammation by promoting rather than terminating effector T cell responses. Summary The transcriptional repressor Blimp-1 acts via a pro-inflammatory IL-10-STAT3 axis as a critical positive regulator of Th2 cells in the lung in response to allergens driving pathophysiology associated with asthma disease.