Thymic stromal lymphopoietin receptor complex (TSLPR complex)

Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that acts as a master regulator of type 2 immune responses (UniProt: Q9HC73). It signals through a heterodimeric receptor complex consisting of the TSLP receptor (TSLPR, also known as CRLF2) and the interleukin-7 receptor alpha (IL-7Rα) chain (NCBI: Gene ID 64109). Binding of TSLP to this complex triggers the activation of Janus kinases (JAK1 and JAK2) and the STAT5 signaling pathway, which promotes the activation of dendritic cells and the differentiation of Th2 cells. This pathway is a major driver of allergic inflammation in diseases such as severe asthma, atopic dermatitis, and chronic obstructive pulmonary disease (COPD) (PMID: 34010520). Therapeutic strategies targeting this complex include monoclonal antibodies like tezepelumab, which binds to the TSLP ligand, preventing its interaction with the receptor and effectively reducing inflammatory biomarkers and clinical exacerbations (PMID: 33979488). Beyond respiratory diseases, the TSLP receptor complex is also implicated in certain hematological malignancies where CRLF2 is overexpressed (PMID: 20075195).

Other names

TSLP receptorCRLF2/IL-7Rα complexCytokine receptor-like factor 2Thymic stromal lymphopoietin receptorTSLPR

Monoclonal antibody-mediated neutralization of the TSLP ligand or competitive blockade of the TSLP receptor complex to inhibit downstream JAK/STAT signaling and type 2 inflammation.