Alpha‐melanocyte stimulating hormone (α‐MSH) induction of Treg cell differentiation

Alpha‐MSH is a potent anti‐inflammatory neuropeptide. We previously reported our discovery that mouse CD4 + T cells primed to function as Th1 cells are suppressed in their expected Th1 functionality when treated with α‐MSH as they were restimulated through their T cell receptor (Tcr). Also, we discovered that the re‐stimulated α‐MSH‐treated primed CD4 + T cells are now TGF‐β‐producing CD25 + Treg cells. We asked whether these α‐MSH‐induced Treg cells express markers and FoxP3 in common with other characterized Treg cells. In addition, we examined the possibility that α‐MSH expands the natural CD25 + Treg cells in the primed CD4 + T cell population. The α‐MSH‐treated Tcr‐stimulated primed CD25 + CD4 + T cells had high expression of CD44 and CTLA‐4, and low expression of CD62L and GITR. The FoxP3 mRNA levels in the CD4 + T cells were 2‐fold enhanced by α‐MSH‐treatment with a parallel decline in high CD127 expression. The depletion of CD25 + cells from the primed CD4 + T cell population before restimulation prevented activation of Th1 cell functionality, but did not change α‐MSH‐induced TGF‐β production. Therefore, α‐MSH‐induces Treg cells that are found in the CD25 + CD4 + T cell population that are not derived from natural CD25 + CD4 + Treg cells. The results suggest that α‐MSH is a potential Treg cell differentiation factor with implications on α‐MSH activity at the resolution of immune responses and in immune homeostasis. Work supported by PHS grant EY10752