Galectin-1 deficiency attenuates imiquimod-induced psoriasiform skin inflammation and is associated with reduced macrophage recruitment.

Introduction: Psoriasis is an immune-mediated inflammatory skin disease in which innate immune activation and the IL-23/IL-17 axis coordinate keratinocyte hyperproliferation and leukocyte recruitment. Galectin-1 (Gal-1) is a glycanbinding protein with context-dependent immunoregulatory effects; however, its function in psoriasiform skin inflammation remains incompletely defined. Methods: Here, we evaluated Gal-1 expression in human psoriasis lesions and investigated its contribution to imiquimod (IMQ)-induced psoriasiform inflammation in mice. Results: Gal-1 immunoreactivity was increased in lesional skin from patients with psoriasis and in IMQ-treated wildtype mice. Compared with IMQ-treated wild-type mice, Gal-1-deficient mice developed less severe erythema, scaling, epidermal thickening, acanthosis, and parakeratosis. Attenuated disease was accompanied by reduced lymphoidorgan enlargement and lower frequencies or numbers of selected innate and adaptive immune-cell populations. In skin, Gal-1 deficiency was associated with reduced macrophage accumulation and diminished CXCL10 mRNA expression, whereas several other inflammatory transcripts showed variable, non-significant trends. In vitro, macrophages from Gal-1 deficient mice displayed impaired migration, while recombinant Gal-1 enhanced macrophage migration in cells from both genotypes. Conclusion: These findings support Gal-1 as a potential therapeutic target for modulating inflammatory-cell recruitment and alleviating psoriasiform skin inflammation.