Adiponectin modulates IL-10 production by T regulatory type 1 cells in allergic inflammation

<bold>Background:</bold> T regulatory type 1 (Tr1) cells are pivotal in maintaining immunological tolerance to allergens in respiratory mucosa, characterized by high IL-10 secretion. Our previous studies showed that, under type 2 (T2) inflammation, adiponectin, through adiponectin receptor 1 (AdipoR1), promotes IL-10 production in Foxp3⁺ T regulatory cells (Tregs). <bold>Aim:</bold> To investigate the effect of adiponectin on IL-10-producing Tr1 cells in allergic inflammation. <bold>Method:</bold> To model allergic lung inflammation, BALB/c mice were sensitised and challenged with ovalbumin (OVA), while control mice were challenged with PBS. Human CD4 T cells were cultured with or without adiponectin under a T2 cytokine milieu. AdipoR1 and IL-10 in murine and human Tr1 cells were assessed by flow cytometry. <bold>Results:</bold> In control mice, lung Tr1 and Foxp3⁺ Tregs exhibited similar levels of AdipoR1; however, a higher frequency of AdipoR1⁺ Tr1 cells was observed in OVA-challenged mice compared to AdipoR1⁺ Foxp3⁺ Tregs <italic>(P<0.001)</italic>. In human peripheral blood, Foxp3⁺ Tregs predominated over Tr1 cells, yet Tr1 cells expressed higher levels of AdipoR1 compared to Foxp3⁺ Tregs <italic>(P<0.05)</italic>. Adiponectin treatment, T2 <italic>in vitro</italic> environment alone or with adiponectin, did not affect AdipoR1 expression. Nevertheless, both intracellular IL-10 in Tr1 cells and the IL-10-producing Tr1/Foxp3⁺ Tregs ratio significantly increased when treated with adiponectin under T2 inflammation <italic>(P<0.001 and P<0.05</italic>, respectively). <bold>Conclusion:</bold> Our findings suggest that adiponectin modulates IL-10 production in Tr1 cells during allergic inflammation, with AdipoR1 potentially playing a crucial role in lung Tr1 cells by increasing the sensitivity to adiponectin.