Lack of canonical thyroid hormone receptor α signaling changes regulatory T cell phenotype in female mice
Christina Wenzek,
Devon Siemes,
G. Sebastian Hönes,
Eva Pastille,
Nina Härting,
Frank Kaiser,
Lars C. Moeller,
Daniel R. Engel,
Astrid M. Westendorf,
Dagmar Führer
Affiliations
Christina Wenzek
Department of Endocrinology, Diabetology and Metabolism, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; Corresponding author
Devon Siemes
Institute for Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
G. Sebastian Hönes
Department of Endocrinology, Diabetology and Metabolism, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Eva Pastille
Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Nina Härting
Institute for Human Genetics, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Frank Kaiser
Institute for Human Genetics, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Lars C. Moeller
Department of Endocrinology, Diabetology and Metabolism, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Daniel R. Engel
Institute for Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Astrid M. Westendorf
Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Dagmar Führer
Department of Endocrinology, Diabetology and Metabolism, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Summary: The immune system has emerged as an important target of thyroid hormones (THs); however, the role of TH in T cells has so far remained elusive. In this study, we assessed the effect of TH receptor α (TRα) signaling on activation and function of T cells. Our findings show that lack of canonical TRα action not only increased the frequency of regulatory T cells (Treg) but propelled an activated and migratory Treg phenotype and nuclear factor κB (NF-κB) activation in Treg. Conversely, canonical TRα action reduced activation of the NF-κB pathway previously shown to play a pivotal role in Treg differentiation and function. Taken together, our findings demonstrate that TRα impacts T cell differentiation and phenotype. Given the well-known interaction of inflammation, immune responses, and TH axis in e.g., severe illness, altered TH-TRα signaling may have an important role in regulating T cell responses during disease.
