G5 Artikkeliväitöskirja
Gene regulation of human T cells: Regulation of T cell differentiation and changes in T cells during progression of Type 1 Diabetes
Tekijät: Biradar, Rahul
Kustannuspaikka: Turku
Julkaisuvuosi: 2026
Sarjan nimi: Annales Universitatis Turkuensis D
Numero sarjassa: 1971
ISBN: 978-952-02-0668-0
eISBN: 978-952-02-0669-7
ISSN: 0355-9483
eISSN: 2343-3213
Julkaisun avoimuus kirjaamishetkellä: Avoimesti saatavilla
Julkaisukanavan avoimuus : Kokonaan avoin julkaisukanava
Verkko-osoite: https://urn.fi/URN:ISBN:978-952-02-0669-7
Tiivistelmä
CD4+ T cells have emerged as the central players of human adaptive immune system where effector and regulatory T cell subsets regulate various immune responses in health as well as during infections. However, when these immune cells are directed towards bodies own cells/tissues through autoantigen, they initiate autoimmune responses in diseases like rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowls disease and type 1 diabetes. Type 1 diabetes is chronic autoimmune disease where immune cells kill the insulin producing beta cells of pancreas. Detection of type 1 diabetes associated autoantibodies is the earliest clinical indication of the disease, it also conveys initiation of autoimmune process in pancreas. While disease associated changes have been detected in immune cells at the onset of disease, less is known about T cell changes that contributes to the initiation of the disease. Effector and regulatory CD4+ T cell subsets are associated with the initiation of autoimmunity. Uncovering disease associated changes in specific CD4+ T cell subsets before autoantibodies appear will help to better understand the disease process for possible immune modulation to delay or cure the disease. The work presented in this dissertation report comprehensive and detailed description of single-cell transcriptome of CD4+ T cell subsets from children progressing to type 1 diabetes, before the appearance of type 1 diabetes associated autoantibodies. The pathogenesis of several autoimmune diseases is linked to proinflammatory effector T cells known as T helper 17 (Th17) cells. Thus, these cells and their key regulatory molecules are being targeted for therapeutic approaches to manipulate Th17 cells in various autoimmune disease. The work presented in the dissertation uncovers new regulators of Th17 cell differentiation. The results indicate both FOSL1 and FOSL2 act synergistically and compete for the binding at BATF occupied loci of the key Th17 genes thus regulating Th17 differentiation. Moreover, epigenetic mechanisms regulate gene expression and the differentiation of Th17 cells. Our results show that a proximal enhancer present in RORA gene regulates Th17 cell differentiation.
CD4+ T cells have emerged as the central players of human adaptive immune system where effector and regulatory T cell subsets regulate various immune responses in health as well as during infections. However, when these immune cells are directed towards bodies own cells/tissues through autoantigen, they initiate autoimmune responses in diseases like rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowls disease and type 1 diabetes. Type 1 diabetes is chronic autoimmune disease where immune cells kill the insulin producing beta cells of pancreas. Detection of type 1 diabetes associated autoantibodies is the earliest clinical indication of the disease, it also conveys initiation of autoimmune process in pancreas. While disease associated changes have been detected in immune cells at the onset of disease, less is known about T cell changes that contributes to the initiation of the disease. Effector and regulatory CD4+ T cell subsets are associated with the initiation of autoimmunity. Uncovering disease associated changes in specific CD4+ T cell subsets before autoantibodies appear will help to better understand the disease process for possible immune modulation to delay or cure the disease. The work presented in this dissertation report comprehensive and detailed description of single-cell transcriptome of CD4+ T cell subsets from children progressing to type 1 diabetes, before the appearance of type 1 diabetes associated autoantibodies. The pathogenesis of several autoimmune diseases is linked to proinflammatory effector T cells known as T helper 17 (Th17) cells. Thus, these cells and their key regulatory molecules are being targeted for therapeutic approaches to manipulate Th17 cells in various autoimmune disease. The work presented in the dissertation uncovers new regulators of Th17 cell differentiation. The results indicate both FOSL1 and FOSL2 act synergistically and compete for the binding at BATF occupied loci of the key Th17 genes thus regulating Th17 differentiation. Moreover, epigenetic mechanisms regulate gene expression and the differentiation of Th17 cells. Our results show that a proximal enhancer present in RORA gene regulates Th17 cell differentiation.
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