TSLPmediated

TSLP-mediated refers to the biological effects and signaling cascades driven by thymic stromal lymphopoietin (TSLP), a cytokine produced predominantly by barrier tissues such as skin, lung, and gut epithelium. TSLP acts as an alarmin that links epithelial barrier disruption to the activation of the immune system, promoting type 2–biased inflammation in susceptible individuals.

The TSLP receptor complex consists of the TSLP receptor (TSLPR, also known as CRLF2) and the IL-7 receptor alpha chain (IL-7Rα). Binding of TSLP to this receptor complex initiates intracellular signaling that engages pathways including JAK-STAT (notably STAT5), MAPK, and PI3K-AKT. Activation of these pathways leads to transcriptional programs that enhance the expression of inflammatory mediators and support Th2-skewed immune responses.

Key cellular targets of TSLP-mediated signaling include dendritic cells, which in turn promote differentiation of naive T cells into Th2 cells; and group 2 innate lymphoid cells (ILC2s), which produce IL-5 and IL-13. TSLP also acts on mast cells, basophils, and B cells, contributing to eosinophilic inflammation and IgE-related responses. Through these actions, TSLP mediates amplification of barrier dysfunction and recruitment of inflammatory cells in tissues.

Clinically, TSLP-mediated pathways are implicated in atopic dermatitis, asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis. Therapies targeting TSLP, such as the monoclonal antibody tezepelumab, have demonstrated efficacy in reducing exacerbations and improving outcomes in severe asthma, underscoring the role of TSLP-mediated signaling in allergic diseases.