FGL-1 Modulates Inter-Organ Communication by Controlling T Cell Homeostasis during the Onset of Sjögren's Disease.

Abstract

OBJECTIVE Autoimmunity occurs due to the tactics between pathogenic and regulatory factors in systemic organs. Although inter-organ 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 inter-organ communication on the cellular or molecular mechanism of autoimmunity using a mouse model of primary Sjögren's disease (pSjD) and patients with pSjD by integrative genomic, bioinformatics, pathological, and immunological analyses. RESULTS Fibrinogen-like protein-1 (FGL-1) was identified as a potent factor for inter-organ communication between the liver and immune system in pSjD model mice. The production of FGL-1 of the liver is induced by IL-6 from CD4+ T cells in these mice. The onset of autoimmune lesions in Fgl1-deficient pSjD model mice was earlier than that in the WT-pSjD model mice. FGL-1 produced in the liver regulates naïve/memory T cell homeostasis. Further, FGL-1 was significantly upregulated 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 inter-organ communication for autoimmune diseases.