Thyrotrophin and thyroxine support immune homeostasis in humans.
Adolescent
Adult
B-Lymphocytes
/ immunology
CD40 Antigens
/ metabolism
Cells, Cultured
Cohort Studies
Female
Homeostasis
Humans
Immunophenotyping
Lymphocyte Activation
Male
Signal Transduction
T-Lymphocyte Subsets
/ immunology
T-Lymphocytes, Regulatory
/ immunology
Thyrotropin
/ metabolism
Thyroxine
/ metabolism
Young Adult
adaptive immunity
immune response
innate immunity
thyroid hormones
thyroid-stimulating hormone (TSH)
Journal
Immunology
ISSN: 1365-2567
Titre abrégé: Immunology
Pays: England
ID NLM: 0374672
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
31
12
2020
received:
03
11
2020
accepted:
04
01
2021
pubmed:
18
1
2021
medline:
5
10
2021
entrez:
17
1
2021
Statut:
ppublish
Résumé
The endocrine and the immune systems interact by sharing receptors for hormones and cytokines, cross-control and feedback mechanisms. To date, no comprehensive study has assessed the impact of thyroid hormones on immune homeostasis. By studying immune phenotype (cell populations, antibody concentrations, circulating cytokines, adipokines and acute-phase proteins, monocyte-platelet interactions and cytokine production capacity) in two large independent cohorts of healthy volunteers of Western European descent from the Human Functional Genomics Project (500FG and 300BCG cohorts), we identified a crucial role of the thyroid hormone thyroxin (T4) and thyroid-stimulating hormone (TSH) on the homeostasis of lymphocyte populations. TSH concentrations were strongly associated with multiple populations of both effector and regulatory T cells, whereas B-cell populations were significantly associated with free T4 (fT4). In contrast, fT4 and TSH had little impact on myeloid cell populations and cytokine production capacity. Mendelian randomization further supported the role of fT4 for lymphocyte homeostasis. Subsequently, using a genomics approach, we identified genetic variants that influence both fT4 and TSH concentrations and immune responses, and gene set enrichment pathway analysis showed enrichment of fT4-affected gene expression in B-cell function pathways, including the CD40 pathway, further supporting the importance of fT4 in the regulation of B-cell function. In conclusion, we show that thyroid function controls the homeostasis of the lymphoid cell compartment. These findings improve our understanding of the immune responses and open the door for exploring and understanding the role of thyroid hormones in the lymphocyte function during disease.
Identifiants
pubmed: 33454989
doi: 10.1111/imm.13306
pmc: PMC8114202
doi:
Substances chimiques
CD40 Antigens
0
Thyrotropin
9002-71-5
Thyroxine
Q51BO43MG4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
155-168Informations de copyright
© 2021 The Authors. Immunology published by John Wiley & Sons Ltd.
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