Endocrine Autoimmune Disease as a Fragility of Immune Surveillance against Hypersecreting Mutants.
Hashimoto’s thyroiditis
autoimmune disease
circuit motif
hyperparathyroidism
hypersecreting adenoma
immune surveillance
primary biliary cirrhosis
systems biology
type 1 diabetes
vitiligo
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
19 05 2020
19 05 2020
Historique:
received:
16
12
2019
revised:
14
02
2020
accepted:
27
04
2020
entrez:
21
5
2020
pubmed:
21
5
2020
medline:
18
11
2020
Statut:
ppublish
Résumé
Some endocrine organs are frequent targets of autoimmune attack. Here, we addressed the origin of autoimmune disease from the viewpoint of feedback control. Endocrine tissues maintain mass through feedback loops that balance cell proliferation and removal according to hormone-driven regulatory signals. We hypothesized the existence of a dedicated mechanism that detects and removes mutant cells that missense the signal and therefore hyperproliferate and hypersecrete with potential to disrupt organismal homeostasis. In this mechanism, hypersecreting cells are preferentially eliminated by autoreactive T cells at the cost of a fragility to autoimmune disease. The "autoimmune surveillance of hypersecreting mutants" (ASHM) hypothesis predicts the presence of autoreactive T cells in healthy individuals and the nature of self-antigens as peptides from hormone secretion pathway. It explains why some tissues get prevalent autoimmune disease, whereas others do not and instead show prevalent mutant-expansion disease (e.g., hyperparathyroidism). The ASHM hypothesis is testable, and we discuss experimental follow-up.
Identifiants
pubmed: 32433950
pii: S1074-7613(20)30180-1
doi: 10.1016/j.immuni.2020.04.022
pmc: PMC7237888
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
872-884.e5Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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