Galectin-9 contributes to the pathogenesis of atopic dermatitis via T cell immunoglobulin mucin-3

• Published in: Frontiers in immunology Vol. 13; p. 952338
• Main Authors: Su, Wenxing, Zhang, Ji, Yang, Shun, Tang, Minhui, Shen, Yu, Liu, Cuiping, Ji, Jiang, Maurer, Marcus, Jiao, Qingqing
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 22.07.2022
• Subjects: Galectin-9 (Gal-9); Immunology; T cell immunoglobulin- and mucin-domain-containing molecules-3 (TIM-3); TH1 cells; TH17 cells; TH2 cells; TH22 cells
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.952338

Background Atopic dermatitis (AD), a common type 2 inflammatory disease, is driven by T helper (T H ) 2/T H 22polarization and cytokines.Galectin-9 (Gal-9), via its receptor T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3), can promote T H 2/T H 22 immunity. The relevance of this in AD is largely unclear. Objectives To characterize the role of TIM-3 and Gal-9 in the pathogenesis of AD and underlying mechanisms. Methods We assessed the expression of Gal-9 and TIM-3 in 30 AD patients, to compare them with those of 30 healthy controls (HC) and to explore possible links with disease features including AD activity (SCORAD), IgE levels, and circulating eosinophils and B cells. We also determined the effects of Gal-9 on T cells from the AD patients. Results Our AD patients had markedly higher levels of serum Gal-9 and circulating TIM-3-expressing T H 1 and T H 17 cells than HC. Gal-9 and TIM-3 were linked to high disease activity, IgE levels, and circulating eosinophils and/or B cells. The rates of circulating TIM-3-positive CD4 + cells were positively correlated with rates of T H 2/T H 22 cells and negatively correlated with rates of T H 1/T H 17 cells. Gal-9 inhibited the proliferation and induced the apoptosis of T cells in patients with AD, especially in those with severe AD. Conclusion Our findings suggest thatGal-9, via TIM-3, contributes to the pathogenesis of AD by augmenting T H 2/T H 22 polarization through the downregulation of T H 1/T H 17immunity. This makes Gal-9 and TIM-3 interesting to explore further, as possible drivers of disease and targets of novel AD treatment.