TSLP-responsive mucosal DCs are critical for the induction of pneumococcal vaccine antigen-specific IgA response in nasal immunization.

Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine involved in Th2-type immune responses, in which myeloid dendritic cells (DCs) are known to be its primary target. However, there is no evidence to date for TSLP-mediated induction and regulation of antibody (Ab) production upon mucosal immunization. Here we found that TSLP and TSLP receptor (TSLPR) expressions were highly up-regulated in mucosal DCs of mice nasally immunized with pneumococcal surface protein A (PspA) plus cholera toxin (CT).  Interestingly, antigen (Ag)-specific IgA, but not IgG Ab responses in both serum and mucosal secretion were significantly reduced in TSLPR-KO mice compared to WT mice following nasal immunization with PspA plus CT. Furthermore, CD11c⁺ mucosal DCs isolated from nasally immunized TSLPR-KO mice were less activated and exhibited a remarkable reduction of IgA enhancing factor expressions (e.g., APRIL, BAFF and TGF-β). Finally, DCs from TSLPR-KO mice given nasal PspA plus CT were less effective for supporting IgA productions in a DC-B cell co-culture system. Taken together, these results suggest that TSLP signaling is pivotal to induce Ag-specific IgA Ab immune responses after nasal immunization with PspA plus CT in mice, which is indispensable for eliciting humoral immunity against pathogenic pnemococcal infections.