近日，以色列魏茨曼科学研究所的Uri Alon小组提出，内分泌自身免疫疾病是免疫系统抵抗超分泌突变细胞的一个弱点。2020年5月19日，《免疫》发表了这一成果。

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

Author: Yael Korem Kohanim, Avichai Tendler, Avi Mayo, Nir Friedman, Uri Alon

Issue&Volume: 2020/05/19

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.

DOI: 10.1016/j.immuni.2020.04.022

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30180-1