New Clues to Immune Dysfunction in Sjögren’s

Sjögren’s disease is an autoimmune disease where the immune system attacks the salivary and lacrimal glands. The result is impaired saliva and tear production, leading to dry mouth and eyes. While this disease is associated with self-reactive immune cells, there are still many unknown mechanisms that contribute to disease progression.

New research deciphers some additional pathways involved in Sjögren’s disease and finds that an immunomodulatory drug currently used to treat rheumatoid arthritis called baricitinib could have some positive effects in Sjögren’s disease.

For the study, they used mice that lacked two genes involved in calcium signaling. When they deleted these genes from regulatory T cells in the mice, they found the mice had symptoms associated with Sjögren’s disease such as dry eyes and month, autoantibodies, immune cells in the salivary glands, and lung inflammation. One thing that the researchers noticed was that because regulatory T cells normally inhibit immune cells, impaired calcium signaling in these cells meant they could not inhibit other immune cells as well. This includes immune cells that produce the pro-inflammatory cytokine interferon gamma. When the researchers deleted the gene for interferon gamma, they found that it improved the function of the salivary gland.

Inhibiting interferon gamma signaling with the drug baricitinib suppressed inflammation in the salivary gland, hinting that the drug could be a potential candidate to treat Sjögren’s disease.

Citation

Wang YH, Li W, McDermott M, et al. IFN-γ-producing TH1 cells and dysfunctional regulatory T cells contribute to the pathogenesis of Sjögren’s disease. Sci Transl Med. 2024;16(778):eado4856. doi:10.1126/scitranslmed.ado4856