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Understanding the molecular regulation of Th17 and Regulatory T Cells in infections and autoimmune diseases

Laufzeit: 01.01.2023 - 31.12.2024

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Kurzfassung


The identification of T helper 17 (Th17) and regulatory T (Treg) cells has markedly improved our understanding of
human immunity under physiological and pathological conditions. Treg cells have a wide immunosuppressive
capacity and play a central role in the maintenance of immune homeostasis, preventing autoimmunity. However, Treg
cells have detrimental effects by aiding the persistence of infectious pathogens and obstructing antitumor immunity.
On the other hand, Th17 cells play a critical role...
The identification of T helper 17 (Th17) and regulatory T (Treg) cells has markedly improved our understanding of
human immunity under physiological and pathological conditions. Treg cells have a wide immunosuppressive
capacity and play a central role in the maintenance of immune homeostasis, preventing autoimmunity. However, Treg
cells have detrimental effects by aiding the persistence of infectious pathogens and obstructing antitumor immunity.
On the other hand, Th17 cells play a critical role in the orchestration of host defense against microbial infections but
are also critical contributors to the pathogenesis of a wide array of autoimmune disorders. A better understanding of
Treg and Th17 biology is critical for the elucidation of the roles of these cells in the pathogenesis of different diseases,
and for the development of novel strategies to treat and prevent immune-related diseases including infections and
autoimmune diseases. Therefore, it is critical to investigate the commitment, plasticity, and interconversion between
Th17 cells and Tregs, and understand the molecular mechanisms responsible for this during infections and
autoimmune diseases. Together, Prof Alves-Filho and Prof Sparwasser labs have recently shown that the stimulator of
interferon genes (STING), a component of the intracellular DNA-sensing pathway, has an intrinsic role of STING in
limiting the Th17 cell pathogenic program. We demonstrate that non-pathogenic Th17 cells express higher levels of
STING than those activated under pathogenic conditions. Activation of STING induces interleukin-10 (IL-10) production
and expression of Foxp3 in Th17 cells, decreasing IL-17A and IL-23R expression (Damasceno et al., Cell Reports, 2022).
Our findings reveal a regulatory function of STING in the Th17 cell activation program, proposing it as a valuable target
to limit Th17 cell-mediated inflammation.
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