Similarities and singularities between innate-like T cell subsets in adults with type 1 diabetes
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Summary Type 1 diabetes (T1D) is an autoimmune disease for which mouse models have highlighted a role for innate-like T cells, although evidence in humans remains limited. Here, we integrated for the first time flow cytometry analyses of invariant natural killer T (iNKT), γδT, and mucosal-associated invariant T (MAIT) cells from the same adults with recent-onset T1D (= 21), long-term T1D (= 47), and healthy controls (= 55). Recent-onset T1D was associated with reduced frequencies of TNFα-producing iNKT and γδT cells, whereas long-term T1D showed more pronounced alterations, including increased PD-1 expression and an exhaustion-like phenotype across all three populations. Principal-component analysis integrating iNKT, γδT, and MAIT cell parameters positioned recent-onset patients between healthy controls and long-term T1D patients. Exploratory predictive modeling suggests that MAIT cell markers may contribute to disease classification. Together, these findings provide an integrated view of innate-like T cell alterations in adult T1D and highlight their relationship with disease duration. abs0010 Graphical abstract http://www.w3.org/1999/xlink float portrait ga1.jpg undfig1 anchor portrait graphical abs0015 Highlights • Innate like-T cells display a common impaired Th1 profile at T1D onset in adults u0010 • Alterations are exacerbated in long-term patients with an exhaustion-like profile u0015 • iNKT, γδT, and MAIT cell phenotypes also present some unique singularities u0020 •
Abstract
Summary Type 1 diabetes (T1D) is an autoimmune disease for which mouse models have highlighted a role for innate-like T cells, although evidence in humans remains limited. Here, we integrated for the first time flow cytometry analyses of invariant natural killer T (iNKT), γδT, and mucosal-associated invariant T (MAIT) cells from the same adults with recent-onset T1D (= 21), long-term T1D (= 47), and healthy controls (= 55). Recent-onset T1D was associated with reduced frequencies of TNFα-producing iNKT and γδT cells, whereas long-term T1D showed more pronounced alterations, including increased PD-1 expression and an exhaustion-like phenotype across all three populations. Principal-component analysis integrating iNKT, γδT, and MAIT cell parameters positioned recent-onset patients between healthy controls and long-term T1D patients. Exploratory predictive modeling suggests that MAIT cell markers may contribute to disease classification. Together, these findings provide an integrated view of innate-like T cell alterations in adult T1D and highlight their relationship with disease duration. abs0010 Graphical abstract http://www.w3.org/1999/xlink float portrait ga1.jpg undfig1 anchor portrait graphical abs0015 Highlights • Innate like-T cells display a common impaired Th1 profile at T1D onset in adults u0010 • Alterations are exacerbated in long-term patients with an exhaustion-like profile u0015 • iNKT, γδT, and MAIT cell phenotypes also present some unique singularities u0020 • Innate-like T cell features represent potential immune-biomarkers in T1D u0025 simple ulist0010 author-highlights abs0020 immunology teaser abs0025