Analysis of factors that regulate effector T cell and regulatory T cell recruitment to the skin

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In this study, we investigated which factors can determine the balance between effector T cells (Teff) and regulator T cells (Treg) in the inflammatory sites. In fixed drug eruption (FDE) lesions that spontaneously resolve, mast cells expressing high levels of IL-16 are abundantly detected, thereby inducing Treg recruitment to the inflammatory site. In contrast, the paucity of mast cells expressing IL-16 in the SJS/TEN lesions that exibit severe immunopathology made Treg impossible to migrate into the inflammatory site. On the other hand, the abundance of mast cells expressing IL-16 was detrimental to tumor regression through the induction of Treg recruitment. Repeated application of imiquimod able to stimulate TLR7/8 caused an increase in IL-17 expressing mast cells and a profound decrease in the Treg/Teff ratio, which was associated with tumor regression. Thus, the balance between Treg and Teff in the inflammatory site can be determined by mast cells resident in the lesion: if they preferentially produce IL-16, the lesions spontaneously resolve; but if they produce IL-17, immunopathology ensues.