Thymic stromal lymphopoietin (TSLP) – pro-inflammatory cytokine and antimicrobial peptide

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine primarily produced by epithelial cells. It functions as a key regulator of immune responses, especially at barrier surfaces such as the skin, gut, and respiratory tract. Humans express two forms of TSLP: long-form TSLP (lfTSLP), which acts as a pro-inflammatory cytokine, and short-form TSLP (sfTSLP), which is an anti-inflammatory antimicrobial peptide. The long-form of TSLP is associated with the development of atopic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, and eosinophilic esophagitis. In addition, TSLP also plays a role in various inflammatory conditions, such as chronic obstructive pulmonary disease, inflammatory bowel disease, and rheumatoid arthritis, as well as neoplastic disorders including acute lymphoblastic leukemia, several lymphomas, and pancreatic and breast cancer. Tezepelumab, a therapeutic antibody that targets TSLP, has been approved for the treatment of severe asthma, and clinical trials are ongoing for other diseases, such as chronic obstructive pulmonary disease. In this review, we focus on the differences between lfTSLP and sfTSLP and the role of single-nucleotide polymorphisms in TSLP. • TSLP mainly expressed by epithelial cells in response to allergens and pathogens. • TSLP orchestrates immune responses at barrier surfaces. • Humans express to TSLP forms: pro-inflammatory lfTSLP and antimicrobial sfTSLP. • Involved in pathogenesis of atopic, inflammatory and malignant diseases • Single-nucleotide polymorphisms in TSLP are associated with several diseases.