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IL-17A/IFN-γ PRODUCING γδ T CELL FUNCTIONAL DICHOTOMY IMPACTS CUTANEOUS LEISHMANIASIS IN MICE
https://www.arca.fiocruz.br/handle/icict/68186
Produção científica do Laboratório de Imunologia Clínica.
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γδ T cells are innate-like lymphocytes with pleiotropic roles in immune responses to pathogens, often ascribed to their IL-17A-producing or IFN-γ-producing γδ T cell subsets. Here we investigated the impact of this functional dichotomy on cutaneous leishmaniasis, a set of neglected diseases caused by parasites of the Leishmania genus. We demonstrate that in Sv129 mice susceptible to Leishmania amazonensis, Vγ4+ γδ T cells are the main source of IL-17A. Furthermore, in type 1 interferon receptor-deficient (A129) mice presenting increased susceptibility to infection, there is a higher frequency of IL-17A-producing γδ T cells when compared to wild-type mice. Mechanistically, we demonstrate that lipophosphoglycan (LPG) of L. amazonensis induces IL-17A-producing γδ T cells. Importantly, C57Bl/6 mice deficient in γδ T cells or in IL-17 receptor (IL-17RA) show reduced lesion sizes, consistent with a pathogenic role of IL-17A-producing γδ T cells in cutaneous leishmaniasis. Conversely, the adoptive transfer of FACS-sorted γδ T cells led to an accumulation of IFN-γ-producing γδ T cells in various susceptible strains of mice which associated with control of lesion development. These data demonstrate a pathophysiological dichotomy in which IL-17A-producing γδ T cells promote pathogenesis, whereas IFN-γ-producing γδ T cells display therapeutic potential in cutaneous leishmaniasis.
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SANTOS, Júlio Souza dos et al. IL-17A/IFN-γ producing γδ T cell functional dichotomy impacts cutaneous leishmaniasis in mice. bioRxiv, p. 1-33, 24 Jan. 2024.DOI
10.1101/2024.01.22.576494Notes
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license (https://creativecommons.org/licenses/by-nd/4.0/).Produção científica do Laboratório de Imunologia Clínica.
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