RT Journal Article
SR Electronic
T1 Endocrine autoimmune disease as a fragility of immune-surveillance against hypersecreting mutants
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 845750
DO 10.1101/845750
A1 Yael Korem Kohanim
A1 Avichai Tendler
A1 Avi Mayo
A1 Nir Friedman
A1 Uri Alon
YR 2019
UL http://biorxiv.org/content/early/2019/11/17/845750.abstract
AB Many endocrine organs show prevalent autoimmune diseases (AID) such as type-1-diabetes and Hashimoto’s-thyroiditis. The fundamental origins of these diseases is unclear. Here we address AID from the viewpoint of feedback control. Endocrine tissues maintain their mass by feedback-loops that balance cell proliferation and removal according to input signals related to the hormone function. Such feedback is unstable to mutant cells that mis-sense the signal, and therefore hyper-proliferate and hyper-secrete the hormone. We hypothesize that in order to prevent these mutants from expanding, each organ has a dedicated ‘autoimmune surveillance of hyper-secreting mutants’ (ASHM), in which hyper-secreting cells are preferentially eliminated, at the cost of a fragility to AID. ASHM correctly predicts the identity of the self-antigens and the presence of T-cells against these self-antigens in healthy individuals. It offers a predictive theory for which tissues get frequent AID, and which do not and instead show frequent mutant-expansion disease (e.g. hyperparathyroidism).