How Lymphatic Drainage Controls Synovial Inflammation

In active synovium of TNF transgenic mice, telocytes are lost, and can be restored with anti-TNF therapy. Electron and confocal microscopy imaging have demonstrated intimate interactions between telocytes and mast cells along lymphatic vessels, leading the team to hypothesize that telocyte signaling to mast cells is essential to histamine release and lymphatic vessel contraction. They further hypothesized and subsequently demonstrated that knocking out telocytes led to a collapsed lymphatic phenotype due to loss of contractile signaling. Telocyte-deficient mice also had a more persistent inflammatory arthritis with greater erosions in a zymosan-induced inflammatory arthritis mouse model.

To summarize the current working model of the synovial lymphatic system and how it drains the joint, Dr. Schwarz said, “there is a telocyte network that extends from telopod to telopod, that parallels the lymphatic vessels from the synovium all the way up to the collecting vessel, where it ends by integrating into mast cells.” Telocytes in the synovium sense osmotic pressure and communicate with mast cells to degranulate and result in a tonic contraction of the vessel.

The model posited two important assumptions, and both were validated experimentally. First, the existence of the network was confirmed via confocal microscopy. Second, investigators demonstrated that telocytes are exquisitely sensitive to osmotic pressure using an in-vitro culture model.

Conclusions

Dr. Schwarz closed with a compelling clinical question: Can exercise maintain or improve telocytes and the synovial lymphatic systemic in chronic inflammatory arthritis? In a mouse model, the answer appears to be yes. He also outlined a working yet intriguing hypothesis that telocytes may differentiate into pro-fibrotic fibroblast like synoviocytes, further contributing to the pathogenesis of inflammatory arthritis.

During the Q&A, attendees posited that there is likely wider application of this model beyond arthritis, such as photosensitivity in lupus. Dr. Schwarz agreed, adding that a similar process may underlie neural injury in multiple sclerosis.

Although further investigation is needed, the work of Dr. Schwarz and his laboratory team highlighted an important piece of the inflammatory arthritis puzzle—one that may someday be a novel therapeutic target.

Michael Cammarata, MD, RhMSUS, is an assistant professor of medicine at the Johns Hopkins University School of Medicine in Baltimore, Md.

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