Abstract:
: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.
journal_name
Immunityjournal_title
Immunityauthors
Korem Kohanim Y,Tendler A,Mayo A,Friedman N,Alon Udoi
10.1016/j.immuni.2020.04.022subject
Has Abstractpub_date
2020-05-19 00:00:00pages
872-884.e5issue
5eissn
1074-7613issn
1097-4180pii
S1074-7613(20)30180-1journal_volume
52pub_type
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