TSLP was initially identified in conditioned medium from a mouse thymic stromal cell line. Human and mouse TSLP are only 43% identical at the amino acid level, and TSLP, like IL-7, exhibits species-specific functions and may function differently in humans and mice. TSLP binds to a heterodimeric receptor constituted by IL-7Ra and TSLPR. TSLPR has low affinity for TSLP, but in combination with IL-7Ra generates a high affinity binding site. TSLP has been associated with the development of allergic disorders in humans, such as asthma, atopic dermatitis, and food allergies. The susceptibility to allergic diseases has been associated to basophil induction by TSLP, and Th2 cytokine production induced by TSLP in mast cells. In addition, TSLP has been associated to the development of Tregs, and blocking TSLPR leads to delayed functional maturation of thymic Tregs. TSLPR has been detected in Tregs from allergic asthmatic patients. TSLP directly activates STAT5 in Tregs and suppresses its suppressive activities; additionally, it inhibits IL-10 production. Human TSLP induces the release of T cell-attracting chemokines (CCL17 and CCL22) from monocytes and enhances the T cell stimulatory capacity of the CD11c+ subset of dendritic cells. TSLP induces proliferation of naïve T cells. In addition, it can drive Th2 differentiation via the induction of IL-4 production, and drives Th2 cytokine-mediated inflammation by acting on bone marrow-resident progenitors, which promotes basophil hematopoiesis. TSLP is upregulated in epithelial cells by IL-1alpha, TNFalpha, and Th2 cytokines.
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