Endocrine Autoimmune Disease as a Fragility of Immune Surveillance against Hypersecreting Mutants.

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

Immunity

journal_title

Immunity

authors

Korem Kohanim Y,Tendler A,Mayo A,Friedman N,Alon U

doi

10.1016/j.immuni.2020.04.022

subject

Has Abstract

pub_date

2020-05-19 00:00:00

pages

872-884.e5

issue

5

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(20)30180-1

journal_volume

52

pub_type

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