Gestational Hypothyroxinemia Affects Its Offspring With a Reduced Suppressive Capacity Impairing the Outcome of the Experimental Autoimmune Encephalomyelitis
Hypothyroxinemia (Hpx) is a thyroid hormone deficiency (THD) condition highly frequent during pregnancy, which although asymptomatic for the mother, it can impair the cognitive function of the offspring. Previous studies have shown that maternal hypothyroidism increases the severity of experimental...
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Frontiers Media S.A.
2018-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01257/full |
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| author | Henny Haensgen Henny Haensgen Eduardo Albornoz Eduardo Albornoz María C. Opazo María C. Opazo Katherinne Bugueño Katherinne Bugueño Evelyn Liliana Jara Fernández Evelyn Liliana Jara Fernández Rebecca Binzberger Tomás Rivero-Castillo Tomás Rivero-Castillo Tomás Rivero-Castillo Luis F. Venegas Salas Luis F. Venegas Salas Felipe Simon Felipe Simon Claudio Cabello-Verrugio Claudio Cabello-Verrugio Alvaro A. Elorza Alvaro A. Elorza Alexis M. Kalergis Alexis M. Kalergis Alexis M. Kalergis Susan M. Bueno Susan M. Bueno Claudia A. Riedel Claudia A. Riedel |
| author_facet | Henny Haensgen Henny Haensgen Eduardo Albornoz Eduardo Albornoz María C. Opazo María C. Opazo Katherinne Bugueño Katherinne Bugueño Evelyn Liliana Jara Fernández Evelyn Liliana Jara Fernández Rebecca Binzberger Tomás Rivero-Castillo Tomás Rivero-Castillo Tomás Rivero-Castillo Luis F. Venegas Salas Luis F. Venegas Salas Felipe Simon Felipe Simon Claudio Cabello-Verrugio Claudio Cabello-Verrugio Alvaro A. Elorza Alvaro A. Elorza Alexis M. Kalergis Alexis M. Kalergis Alexis M. Kalergis Susan M. Bueno Susan M. Bueno Claudia A. Riedel Claudia A. Riedel |
| author_sort | Henny Haensgen |
| collection | DOAJ |
| description | Hypothyroxinemia (Hpx) is a thyroid hormone deficiency (THD) condition highly frequent during pregnancy, which although asymptomatic for the mother, it can impair the cognitive function of the offspring. Previous studies have shown that maternal hypothyroidism increases the severity of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model for multiple sclerosis (MS). Here, we analyzed the immune response after EAE induction in the adult offspring gestated in Hpx. Mice gestated in Hpx showed an early appearance of EAE symptoms and the increase of all parameters of the disease such as: the pathological score, spinal cord demyelination, and immune cell infiltration in comparison to the adult offspring gestated in euthyroidism. Isolated CD4+CD25+ T cells from spleen of the offspring gestated in Hpx that suffer EAE showed reduced capacity to suppress proliferation of effector T cells (TEff) after being stimulated with anti-CD3 and anti-CD28 antibodies. Moreover, adoptive transfer experiments of CD4+CD25+ T cells from the offspring gestated in Hpx suffering EAE to mice that were induced with EAE showed that the receptor mice suffer more intense EAE pathological score. Even though, no significant differences were detected in the frequency of Treg cells and IL-10 content in the blood, spleen, and brain between mice gestated in Hpx or euthyroidism, T cells CD4+CD25+ from spleen have reduced capacity to differentiate in vitro to Treg and to produce IL-10. Thus, our data support the notion that maternal Hpx can imprint the immune response of the offspring suffering EAE probably due to a reduced capacity to trigger suppression. Such “imprints” on the immune system could contribute to explaining as to why adult offspring gestated in Hpx suffer earlier and more intense EAE. |
| first_indexed | 2024-04-14T02:39:33Z |
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| id | doaj.art-e5744f5a2b6e4fef84d314b937121829 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T02:39:33Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e5744f5a2b6e4fef84d314b9371218292022-12-22T02:17:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-06-01910.3389/fimmu.2018.01257326010Gestational Hypothyroxinemia Affects Its Offspring With a Reduced Suppressive Capacity Impairing the Outcome of the Experimental Autoimmune EncephalomyelitisHenny Haensgen0Henny Haensgen1Eduardo Albornoz2Eduardo Albornoz3María C. Opazo4María C. Opazo5Katherinne Bugueño6Katherinne Bugueño7Evelyn Liliana Jara Fernández8Evelyn Liliana Jara Fernández9Rebecca Binzberger10Tomás Rivero-Castillo11Tomás Rivero-Castillo12Tomás Rivero-Castillo13Luis F. Venegas Salas14Luis F. Venegas Salas15Felipe Simon16Felipe Simon17Claudio Cabello-Verrugio18Claudio Cabello-Verrugio19Alvaro A. Elorza20Alvaro A. Elorza21Alexis M. Kalergis22Alexis M. Kalergis23Alexis M. Kalergis24Susan M. Bueno25Susan M. Bueno26Claudia A. Riedel27Claudia A. Riedel28Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Santiago, ChileDepartamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Santiago, ChileDepartamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Santiago, ChileDepartamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Santiago, ChileDepartamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileMedizinishen Fakultät, Eberhard Karls Universität, Tübingen, GermanyMillennium Institute on Immunology and Immunotherapy, Santiago, ChileDepartamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileDepartamento Biomédico, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta, ChileDepartamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Santiago, ChileDepartamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Santiago, ChileDepartamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Santiago, ChileCentro de Investigaciones Biomédicas, Facultad de Ciencias de la Vida y Facultad de Medicina, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Santiago, ChileDepartamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileDepartamento de Endocrinología, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Santiago, ChileDepartamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileDepartamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Santiago, ChileHypothyroxinemia (Hpx) is a thyroid hormone deficiency (THD) condition highly frequent during pregnancy, which although asymptomatic for the mother, it can impair the cognitive function of the offspring. Previous studies have shown that maternal hypothyroidism increases the severity of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model for multiple sclerosis (MS). Here, we analyzed the immune response after EAE induction in the adult offspring gestated in Hpx. Mice gestated in Hpx showed an early appearance of EAE symptoms and the increase of all parameters of the disease such as: the pathological score, spinal cord demyelination, and immune cell infiltration in comparison to the adult offspring gestated in euthyroidism. Isolated CD4+CD25+ T cells from spleen of the offspring gestated in Hpx that suffer EAE showed reduced capacity to suppress proliferation of effector T cells (TEff) after being stimulated with anti-CD3 and anti-CD28 antibodies. Moreover, adoptive transfer experiments of CD4+CD25+ T cells from the offspring gestated in Hpx suffering EAE to mice that were induced with EAE showed that the receptor mice suffer more intense EAE pathological score. Even though, no significant differences were detected in the frequency of Treg cells and IL-10 content in the blood, spleen, and brain between mice gestated in Hpx or euthyroidism, T cells CD4+CD25+ from spleen have reduced capacity to differentiate in vitro to Treg and to produce IL-10. Thus, our data support the notion that maternal Hpx can imprint the immune response of the offspring suffering EAE probably due to a reduced capacity to trigger suppression. Such “imprints” on the immune system could contribute to explaining as to why adult offspring gestated in Hpx suffer earlier and more intense EAE.https://www.frontiersin.org/article/10.3389/fimmu.2018.01257/fullhypothyroxinemiaT regulatory cellsmultiple sclerosispregnancyexperimental autoimmune encephalomyelitis |
| spellingShingle | Henny Haensgen Henny Haensgen Eduardo Albornoz Eduardo Albornoz María C. Opazo María C. Opazo Katherinne Bugueño Katherinne Bugueño Evelyn Liliana Jara Fernández Evelyn Liliana Jara Fernández Rebecca Binzberger Tomás Rivero-Castillo Tomás Rivero-Castillo Tomás Rivero-Castillo Luis F. Venegas Salas Luis F. Venegas Salas Felipe Simon Felipe Simon Claudio Cabello-Verrugio Claudio Cabello-Verrugio Alvaro A. Elorza Alvaro A. Elorza Alexis M. Kalergis Alexis M. Kalergis Alexis M. Kalergis Susan M. Bueno Susan M. Bueno Claudia A. Riedel Claudia A. Riedel Gestational Hypothyroxinemia Affects Its Offspring With a Reduced Suppressive Capacity Impairing the Outcome of the Experimental Autoimmune Encephalomyelitis Frontiers in Immunology hypothyroxinemia T regulatory cells multiple sclerosis pregnancy experimental autoimmune encephalomyelitis |
| title | Gestational Hypothyroxinemia Affects Its Offspring With a Reduced Suppressive Capacity Impairing the Outcome of the Experimental Autoimmune Encephalomyelitis |
| title_full | Gestational Hypothyroxinemia Affects Its Offspring With a Reduced Suppressive Capacity Impairing the Outcome of the Experimental Autoimmune Encephalomyelitis |
| title_fullStr | Gestational Hypothyroxinemia Affects Its Offspring With a Reduced Suppressive Capacity Impairing the Outcome of the Experimental Autoimmune Encephalomyelitis |
| title_full_unstemmed | Gestational Hypothyroxinemia Affects Its Offspring With a Reduced Suppressive Capacity Impairing the Outcome of the Experimental Autoimmune Encephalomyelitis |
| title_short | Gestational Hypothyroxinemia Affects Its Offspring With a Reduced Suppressive Capacity Impairing the Outcome of the Experimental Autoimmune Encephalomyelitis |
| title_sort | gestational hypothyroxinemia affects its offspring with a reduced suppressive capacity impairing the outcome of the experimental autoimmune encephalomyelitis |
| topic | hypothyroxinemia T regulatory cells multiple sclerosis pregnancy experimental autoimmune encephalomyelitis |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01257/full |
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