Targeting Interleukin-7 Signalling in Ulcerative Colitis: Rationale and Emerging Clinical Evidence
Abstract
Ulcerative colitis (UC) remains difficult to control in a substantial proportion of patients despite an expanding range of advanced therapies. Interleukin-7 (IL-7) is a homeostatic cytokine that supports lymphocyte survival, persistence and intestinal trafficking through signalling via IL-7 receptor-α (IL-7Rα; CD127), providing a rationale for selective pathway inhibition in chronic intestinal inflammation. This narrative review examines the biology of IL-7/IL-7R signalling in inflammatory bowel disease (IBD) and summarises the preclinical, translational and clinical development of lusvertikimab, a humanised monoclonal antibody targeting IL-7Rα. MEDLINE was searched from inception to 31 July 2026, supplemented by reference-list screening, trial registries, conference proceedings and regulatory sources. Experimental studies show that IL-7 supports the persistence of colitogenic effector-memory T cells and contributes to innate immune activation. Human translational data demonstrate enrichment of IL-7R pathway activity in treatment-refractory IBD, association with anti-TNF non-response, and IL-7-mediated upregulation of the gut-homing integrin α4β7. Preclinical IL-7R blockade attenuated experimental colitis, reduced intestinal T-cell trafficking and altered inflammatory responses in UC tissue. In a first-in-human study, lusvertikimab produced sustained receptor occupancy and suppression of IL-7-associated gene expression without broad lymphocyte depletion. In the phase II…
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