Year: 2025
Type: article
Abstract: 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)
Source: The Journal of Immunology
Institution: La Jolla Institute for Immunology
Language: English
Subfield: Dermatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Hedgehog signalling in T cell effector and memory function in vivo., G279312593, University of Cambridge Translational Partnership Award, HEDGEMOD - HEDGEhog signalling MODes of immune cells in health and disease, G3665773225, G4471531365, G6477683973, G6598984234, G6868616705, G6976145177, G7626029692, G7696472789, Cambridge Stem Cell Institute
OpenAlex ID: W4416448756
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