Hypothyroidism-associated immunosuppression involves induction of galectin1-producing regulatory T cells
Abstract: 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...
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| Formato: | Artículo |
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Wiley
2023
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| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/16733 |
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I33-R139-123456789-167332024-03-26T11:10:06Z Hypothyroidism-associated immunosuppression involves induction of galectin1-producing regulatory T cells Valli, Eduardo Dalotto Moreno, Tomás Sterle, Helena Andrea Méndez Huergo, Santiago P. Paulazo, Maria Alejandra García, Silvia I. Pirola, Carlos J. Klecha, Alicia Juana Rabinovich, Gabriel A. Cremaschi, Graciela A. HIPOTIROIDISMO LINFOCITOS T REGULADORES GALECTINA-1 TIROTROPINA HORMONA LIBERADORA DE TIROTROPINA Abstract: 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. 2023-07-11T14:33:48Z 2023-07-11T14:33:48Z 2023 Artículo Valli, 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 1530-6860 (online) https://repositorio.uca.edu.ar/handle/123456789/16733 10.1096/fj.202200884R 36934391 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley The FASEB Journal vol.37, No.4, 2023 |
| institution |
Universidad Católica Argentina |
| institution_str |
I-33 |
| repository_str |
R-139 |
| collection |
Repositorio Institucional de la Universidad Católica Argentina (UCA) |
| language |
Inglés |
| topic |
HIPOTIROIDISMO LINFOCITOS T REGULADORES GALECTINA-1 TIROTROPINA HORMONA LIBERADORA DE TIROTROPINA |
| spellingShingle |
HIPOTIROIDISMO LINFOCITOS T REGULADORES GALECTINA-1 TIROTROPINA HORMONA LIBERADORA DE TIROTROPINA Valli, Eduardo Dalotto Moreno, Tomás Sterle, Helena Andrea Méndez Huergo, Santiago P. Paulazo, Maria Alejandra García, Silvia I. Pirola, Carlos J. Klecha, Alicia Juana Rabinovich, Gabriel A. Cremaschi, Graciela A. Hypothyroidism-associated immunosuppression involves induction of galectin1-producing regulatory T cells |
| topic_facet |
HIPOTIROIDISMO LINFOCITOS T REGULADORES GALECTINA-1 TIROTROPINA HORMONA LIBERADORA DE TIROTROPINA |
| description |
Abstract: 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. |
| format |
Artículo |
| author |
Valli, Eduardo Dalotto Moreno, Tomás Sterle, Helena Andrea Méndez Huergo, Santiago P. Paulazo, Maria Alejandra García, Silvia I. Pirola, Carlos J. Klecha, Alicia Juana Rabinovich, Gabriel A. Cremaschi, Graciela A. |
| author_facet |
Valli, Eduardo Dalotto Moreno, Tomás Sterle, Helena Andrea Méndez Huergo, Santiago P. Paulazo, Maria Alejandra García, Silvia I. Pirola, Carlos J. Klecha, Alicia Juana Rabinovich, Gabriel A. Cremaschi, Graciela A. |
| author_sort |
Valli, Eduardo |
| title |
Hypothyroidism-associated immunosuppression involves induction of galectin1-producing regulatory T cells |
| title_short |
Hypothyroidism-associated immunosuppression involves induction of galectin1-producing regulatory T cells |
| title_full |
Hypothyroidism-associated immunosuppression involves induction of galectin1-producing regulatory T cells |
| title_fullStr |
Hypothyroidism-associated immunosuppression involves induction of galectin1-producing regulatory T cells |
| title_full_unstemmed |
Hypothyroidism-associated immunosuppression involves induction of galectin1-producing regulatory T cells |
| title_sort |
hypothyroidism-associated immunosuppression involves induction of galectin1-producing regulatory t cells |
| publisher |
Wiley |
| publishDate |
2023 |
| url |
https://repositorio.uca.edu.ar/handle/123456789/16733 |
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1807949192040022016 |