Autoimmune CD4+T cells Cause Meibomian Gland Dysfunction

ABSTRACT: Sjögren disease (SjD) is the prototype autoimmune dry eye disease driven by an autoreactive CD4+T cell-mediated immune response that attacks lacrimal and salivary glands. Meibomian glands are lipid-producing glands on 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 MGD. Herein, we investigated whether autoreactive CD4+T cells induce MGD and characterized the pathophysiologic mechanisms using an adoptive transfer (AT) model. T cells were isolated from CD25KO (CD4KO) or wild-type mice (CD4WT) and transferred into RAG1KO mice and compared with CD4KO co-adoptively transferred with WT Tregs (CD4KO+TregsWT). Our results showed that CD4KO recipients showed MG dropout, CD4+IFN-γ+ infiltration, increased MHC II presentation in the periglandular area, MG fibrosis, and decreased lipid production. These changes were accompanied by significant transcriptomic changes in the tarsal plates, with Type II Interferon as the top pathway. CD4KO+TregsWT recipients had minimal inflammation. These results indicate that autoimmune CD4+T cells are sufficient to cause MGD, and, healthy young Tregs can prevent this 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE314353 | GEO | 2026/10/05

REPOSITORIES: GEO