Regulatory Role of FGL-1 in Interorgan Communication by Controlling T Cell Homeostasis During the Onset of Sjögren Disease.

Abstract

OBJECTIVE: Autoimmunity occurs due to the tactics between pathogenic and regulatory factors in systemic organs. Although interorgan communication has been demonstrated in various diseases, the effects of the crosstalk between the immune system and other organs on autoimmune disease is unknown. METHODS: We analyzed the influence of interorgan communication on the cellular or molecular mechanism of autoimmunity using a mouse model of primary Sjögren disease (pSjD) and patients with pSjD by integrative genomic, bioinformatic, pathologic, and immunologic analyses. RESULTS: Fibrinogen-like protein-1 (FGL-1) was identified as a potent factor for interorgan communication between the liver and immune system in pSjD model mice. The production of FGL-1 of the liver is induced by interleukin-6 (IL-6) from CD4T cells in these mice. The onset of autoimmune lesions in an Fgl1-deficient pSjD model mice was earlier than that in the wild type pSjD model mice. FGL-1 produced in the liver regulates naïve and memory T cell homeostasis. Further, FGL-1 was significantly up-regulated in patients with pSjD compared to the controls. Moreover, its concentration was closely related to the serum IL-6 levels in patients with pSjD. CONCLUSION: FGL-1 plays a key role in the onset of autoimmunity by suppressing T cell activation in pSjD. Our results will facilitate the development of novel diagnostic or therapeutic strategies targeting the interorgan communication for autoimmune diseases.