Autoimmune CD4 ⁺ T cells Cause Meibomian Gland Dysfunction

Area of Science:

• Immunology
• Ophthalmology
• Autoimmune Diseases

Background:

• Sjögren disease (SjD) is an autoimmune condition primarily affecting exocrine glands.
• Autoreactive CD4+ T cells are known drivers of lacrimal gland destruction in SjD.
• The role of T cells in meibomian gland dysfunction (MGD) remains unclear.

Purpose of the Study:

• To investigate if autoreactive CD4+ T cells can induce MGD.
• To characterize the underlying pathophysiological mechanisms of T-cell-induced MGD.
• To determine the potential protective role of regulatory T cells.

Main Methods:

• Adoptive transfer model using T cells from CD25KO (CD4 KO) or wild-type (CD4 WT) mice into Rag1 KO mice.
• Co-transfer of CD4 KO cells with wild-type regulatory T cells (CD4 KO + Tregs WT).
• Analysis of meibomian gland pathology, immune cell infiltration, and molecular pathways.

Main Results:

• CD4 KO recipients developed MGD, characterized by gland dropout, CD4+ IFN-γ+ T cell infiltration, and fibrosis.
• Increased MHC II presentation and Type II interferon signaling were observed in affected glands.
• Minimal inflammation was noted in Rag1 KO, CD4 WT, and CD4 KO + Tregs WT recipients.

Conclusions:

• Autoreactive CD4+ T cells are sufficient to cause MGD, independent of lacrimal gland involvement.
• Regulatory T cells can prevent T-cell-mediated MGD.
• Findings provide mechanistic insights into Sjögren disease pathogenesis and potential therapeutic targets.