IL-17A/IFN-γ producing γδ T cell functional dichotomy impacts cutaneous leishmaniasis in mice.

Autor:	Souza Dos-Santos J; Immunobiotechnology Laboratory, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.; Clinical Immunology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-360, RJ, Brazil., Firmino-Cruz L; Mucosal B cell Laboratory, Department of Pathology, New York University Langone Medical Center, 550 1st Ave., New York, NY 10016, USA., Oliveira-Maciel D; Immunobiotechnology Laboratory, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.; Clinical Immunology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-360, RJ, Brazil., Marcia da Fonseca-Martins A; Immunobiotechnology Laboratory, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.; Clinical Immunology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-360, RJ, Brazil., Diniz Ramos T; Immunobiotechnology Laboratory, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.; Clinical Immunology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-360, RJ, Brazil., Nunes-Sousa L; Immunobiotechnology Laboratory, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.; Clinical Immunology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-360, RJ, Brazil., Bittencourt Dos Santos I; Immunobiotechnology Laboratory, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.; Clinical Immunology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-360, RJ, Brazil., Pedro Soares R; Instituto René Rachou, Fiocruz, Belo Horizonte, MG, Brazil., Claudio Oliveira Gomes D; Núcleo de Doenças Infecciosas/Núcleo de Biotecnologia, Universidade Federal do Espírito Santo., Mengel J; Clinical Immunology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-360, RJ, Brazil., Silva-Santos B; Institute of Molecular Medicine João Lobo Antunes, Faculty of Medicine of the University of Lisbon, 1649-028 Lisbon, Portugal., de Matos Guedes HL; Immunobiotechnology Laboratory, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.; Clinical Immunology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-360, RJ, Brazil.
Jazyk:	angličtina
Zdroj:	Journal of leukocyte biology [J Leukoc Biol] 2024 Dec 04. Date of Electronic Publication: 2024 Dec 04.
DOI:	10.1093/jleuko/qiae251
Abstrakt:	γδ T cells play diverse roles in immune responses, producing either IL-17A or IFN-γ. Here we investigated the impact of this functional dichotomy on cutaneous leishmaniasis. We demonstrate that in Sv129 mice susceptible to Leishmania amazonensis, Vγ4+ γδ T cells are the main source of IL-17A. In type 1 interferon receptor-deficient (A129) mice with heightened susceptibility, there is an increased frequency of IL-17A-producing γδ T cells. L. amazonensis's lipophosphoglycan induces these IL-17A-producing γδ T cells. Notably, C57Bl/6 mice deficient in γδ T cells or IL-17 receptor exhibit smaller lesions, indicating a pathogenic role of IL-17A-producing γδ T cells in cutaneous leishmaniasis. Conversely, adoptive transfer of FACS-sorted γδ T cells lead to an accumulation of IFN-γ-producing γδ T cells, associated with control of lesion development. On the other hand, adoptive transfer of FACS-sorted IFN- γ- deficient-γδ T cells abolished the control of lesion development. These data demonstrate a pathophysiological dichotomy where IL-17A-producing γδ T cells promote pathogenesis, while IFN-γ-producing γδ T cells offer therapeutic potential in cutaneous leishmaniasis. (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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