CD30L blockade attenuates atopic dermatitis skin inflammation 2425

Description Inhibiting IL-13 has proven to be very effective in patients with Th2-biased atopic dermatitis (AD). Additionally, recent successes in clinical trials targeting the T cell costimulatory molecules OX40 and OX40L (TNFSF4) indicate that these co-stimulatory pathways may provide promising new treatment options for AD. Using in silico and in vivo approaches we determined that targeting another T cell costimulatory molecule, CD30L (TNFSF8), could also serve as a potential treatment option for AD. Analysis of multiple scRNA-seq datasets from skin lesions of AD patients showed that CD30 or CD30L were co-expressed with OX40 or OX40L in T cell clusters expressing IL13 and/or IL22 transcripts. Suggesting therapeutic relevance, experimental mice prophylactically injected with an anti-CD30L antibody did not develop full allergen-induced AD characteristics including reduced epidermal hyperplasia, immune cell infiltration, and expression of AD-related genes, similar to the effects observed with an anti-IL-13 antibody. Furthermore, therapeutic inhibition of CD30L in mice with AD also attenuated all of the above features comparable to blocking OX40L. Together, the human and mouse data suggest that the CD30-CD30L axis could be a promising target for future therapeutic interventions in human AD, similar to the OX40-OX40L axis. Funding Sources supported by commercial sponsored research funds from Bristol Myers Squibb and LJI institutional funds. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)