AUTHOR=Su Wenxing , Zhang Ji , Yang Shun , Tang Minhui , Shen Yu , Liu Cuiping , Ji Jiang , Maurer Marcus , Jiao Qingqing 

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.952338

DOI=10.3389/fimmu.2022.952338

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Atopic dermatitis (AD), a common type 2 inflammatory disease, is driven by T helper (T<sub>H</sub>) 2/T<sub>H</sub>22polarization and cytokines.Galectin-9 (Gal-9), <italic>via</italic> its receptor T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3), can promote T<sub>H</sub>2/T<sub>H</sub>22 immunity. The relevance of this in AD is largely unclear.</p></sec><sec><title>Objectives</title><p>To characterize the role of TIM-3 and Gal-9 in the pathogenesis of AD and underlying mechanisms.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>Our AD patients had markedly higher levels of serum Gal-9 and circulating TIM-3-expressing T<sub>H</sub>1 and T<sub>H</sub>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<sup>+</sup> cells were positively correlated with rates of T<sub>H</sub>2/T<sub>H</sub>22 cells and negatively correlated with rates of T<sub>H</sub>1/T<sub>H</sub>17 cells. Gal-9 inhibited the proliferation and induced the apoptosis of T cells in patients with AD, especially in those with severe AD.</p></sec><sec><title>Conclusion</title><p>Our findings suggest thatGal-9, <italic>via</italic> TIM-3, contributes to the pathogenesis of AD by augmenting T<sub>H</sub>2/T<sub>H</sub>22 polarization through the downregulation of T<sub>H</sub>1/T<sub>H</sub>17immunity. This makes Gal-9 and TIM-3 interesting to explore further, as possible drivers of disease and targets of novel AD treatment.</p></sec>