A novel polypeptide molecule attenuates atopic dermatitis by targeting CCR8-CCL1 axis

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with diverse clinical phenotypes. Although a variety of drugs are available, the current clinical treatment still cannot meet the needs of patients with AD. In this study, we designed a series of polypeptides through a new drug discovery technology combined with big data and artificial intelligence in our polypeptide library and successfully screened 2 candidates by in vitro and in vivo study. As results showed that the 2 candidates have a high affinity for human CC chemokine receptor 8 (CCR8) and significantly inhibited interstitial dendritic cell (iDC) migration induced by CC chemokine ligand 1 (CCL1) via interfering with the CCL1-CCR8 axis. The efficacy of CCR8 polypeptide candidates on AD were further evaluated in two dermatitis mouse models. We found that applying SP-TG02 to the skin ameliorated MC903 and OXA-induced skin AD-like symptoms and histological damage, reduced mast cell infiltration and down-regulated the expression of pro-inflammatory cytokines in skin tissue. Collectively, SP-TG02 may be a promising novel CCR8 polypeptide inhibitor for the treatment of atopic dermatitis.