Mast cell differentiation is operated by a T cell response (#339)
After exposure to an allergen, mast cells (MCs) accumulate at the allergic site and then act as effector cells of inflammation. Despite many investigations into of the role of MCs in allergic inflammation, the mechanism underlying the expansion of these cells under allergic inflammatory conditions remains unclear.
When splenocytes from mice immunized with OVA or KLH were repeatedly stimulated in vitro with antigens, expansion of MCs was greater than that of antigen-specific T cells for up to 3 weeks. This observation raised the possibility that T cell responses elicited by the antigens were associated with MC development. To verify this, purified splenic T cells from immunized mice were cocultured with MCs or various progenitor populations and repeatedly stimulated with antigens. The results obtained from these coculture experiments suggested that T cell responses could have an effect on myeloid progenitors and act to drive the MC differentiation. Additionally, IL-3 from T cells was crucial for MC differentiation. To validate whether MC differentiation that we observed in in vitro culture experiments might also occur in allergic disease, we used a murine food allergy model that was dependent on T cells and displayed an accumulation of MCs the colon, and found that this murine model exhibited the accumulation of myeloid progenitors and the up-regulation of IL-3.
Collectively, our study suggests that T cell responses against allergens may drive MC differentiation to generate effector cells of allergic inflammation. Blocking this differentiation pathway may be an attractive therapeutic strategy for treating allergic inflammation.