Autoimmune CD4+T cells Cause Meibomian Gland Dysfunction

Abstract

Sjogren disease (SjD) is an autoimmune disease driven by autoreactive CD4+T cells that leads to an immune-mediated loss of lacrimal glands. Meibomian glands are lipid-producing glands in the eyelids that help prevent tear evaporation. While the role of T cells in lacrimal gland-mediated destruction is well established, it is unknown whether pathogenic T cells can cause MG dysfunction (MGD). Herein, we investigated whether autoreactive CD4+T cells induce MGD and characterized the pathophysiologic mechanisms using an adoptive transfer model. T cells were isolated from CD25KO (CD4KO) or wild-type (CD4WT) mice, transferred into Rag1KO mice. Further, CD4KO cells were co-adoptively transferred with WT regulatory T cells (CD4KO+TregsWT). Our results demonstrate that CD4KO recipients had MG dropout, CD4+IFN-{gamma}+ infiltration, increased MHC II presentation within the periglandular area, MG fibrosis, and decreased lipid production and upregulation of pathways related to inflammation, including Type II interferon signaling. Rag1KO, CD4WT, and CD4KO+TregsWT recipients exhibited minimal inflammation in the periglandular MG area. These results indicate that autoimmune CD4+T cells are sufficient to cause MGD, and healthy young regulatory T cells can prevent T-cell-mediated damage. Taken together, our findings provide mechanistic insights into the pathogenesis autoimmune SjD, and could impact how patients are managed in the clinic.