Hypothyroidism-associated immunosuppression involves induction of galectin1-producing regulatory T cells

dc.creatorValli, Eduardo
dc.creatorDalotto Moreno, Tomás
dc.creatorSterle, Helena A.
dc.creatorMéndez Huergo, Santiago P.
dc.creatorPaulazo, María A.
dc.creatorGarcía, Silvia I.
dc.creatorPirola, Carlos J.
dc.creatorKlecha, Alicia J.
dc.creatorRabinovich, Gabriel A.
dc.creatorCremaschi, Graciela A.
dc.date2023-07-11T14:33:48Z
dc.date2023-07-11T14:33:48Z
dc.date2023
dc.date.accessioned2023-08-30T15:41:25Z
dc.date.available2023-08-30T15:41:25Z
dc.identifierValli, E. et al. Hypothyroidism-associated immunosuppression involves induction of galectin1-producing regulatory T cells [en línea]. Postprint de artículo publicado en The FASEB Journal. 2023, 37 (4). doi:10.1096/fj.202200884R. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/16733
dc.identifier1530-6860 (online)
dc.identifierhttps://repositorio.uca.edu.ar/handle/123456789/16733
dc.identifier10.1096/fj.202200884R
dc.identifier36934391
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8526871
dc.descriptionAbstract: Hypothyroidism exerts deleterious effects on immunity, but the precise role of the hypothalamicpituitary-thyroid (HPT) axis in immunoregulatory and tolerogenic programs is barely understood. Here we investigated the mechanisms underlying hypothyroid-related immunosuppression by examining the regulatory role of components of the HPT axis. We first analyzed lymphocyte activity in mice overexpressing the TRH gene (Tg-Trh). T cells from TgTrh showed increased proliferation than wild type (WT) euthyroid mice in response to polyclonal activation. The release of Th1 proinflammatory cytokines was also increased in TgTrh, and TSH levels correlated with T cell proliferation. To gain further mechanistic insights into hypothyroidism-related immunosuppression, we evaluated T cell subpopulations in lymphoid tissues of hypothyroid and control mice. No differences were observed in CD3/CD19 or CD4/CD8 ratios between these strains. However, the frequency of regulatory T cells (Tregs) was significantly increased in hypothyroid mice, and not in Tg-Trh mice. Accordingly, in vitro Tregs differentiation was more pronounced in naïve T cells isolated from hypothyroid mice. Since Tregs overexpress galectin-1 (Gal-1) and mice lacking this lectin (Lgals1-/-) show reduced Treg function, we investigated the involvement of this immunoregulatory lectin in the control of Tregs in settings of hypothyroidism. Increased T lymphocyte reactivity and reduced frequency of Tregs were found in hypothyroid Lgals1-/- mice when compared to hypothyroid WT animals. This effect was rescued by addition of recombinant Gal-1. Finally, increased expression of Gal-1 was found in Tregs purified from hypothyroid WT mice compared with their euthyroid counterpart. Thus, a substantial increase in the frequency and activity of Gal-1-expressing Tregs underlies immunosuppression associated with hypothyroid conditions, with critical implications in immunopathology, metabolic disorders, and cancer.
dc.formatapplication/pdf
dc.languageeng
dc.publisherWiley
dc.rightsAcceso abierto
dc.rightshttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.sourceThe FASEB Journal vol.37, No.4, 2023
dc.subjectHIPOTIROIDISMO
dc.subjectLINFOCITOS T REGULADORES
dc.subjectGALECTINA-1
dc.subjectTIROTROPINA
dc.subjectHORMONA LIBERADORA DE TIROTROPINA
dc.titleHypothyroidism-associated immunosuppression involves induction of galectin1-producing regulatory T cells
dc.typeArtículo


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