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

BackgroundAtopic 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. ObjectivesTo characterize the role of TIM-3 and Gal-9 in the pathogenesis of AD and underlying mechanisms. MethodsWe 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. ResultsOur 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. ConclusionOur 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.