Background/Purpose: Sjögren’s syndrome (SjS) is a chronic autoimmune disease primarily involving the exocrine glands where the involvement of the innate immune system is largely uncharacterized. Mer signaling has been found to be protective in several autoimmune diseases but remains unstudied in SjS. Here, we sought to investigate the protective capacity of Mer signaling in SjS.

Methods: SjS patient sera was evaluated for levels of soluble, inactivated Mer (sMer) via ELISA and sMer levels were correlated to disease manifestations. C57BL/6.NOD-Aec1Aec2 (SjS^S) mice were assessed for sMer levels, TACE activity, and Mer signaling outcomes. SjS diagnostic criteria were examined in MerKO mice.

Results: sMer levels were elevated in SjS patient sera and positively correlated with focus score, ocular staining scores, rheumatoid factor, and Ro60 autoantibody levels. Increased sMer was also detected in SjS^S mouse sera, coinciding with higher TACE activity, the enzyme responsible for cleavage of Mer, and inactivation of such. Mer signaling outcomes were observed to be diminished in SjS^S mice as evidenced by impaired efferocytosis in SjS^S mouse macrophages and decreased Socs1 and Socs3 expression in SjS^S salivary gland (SG). MerKO mice developed SG infiltrates of B and T lymphocytes, SG apoptotic cells, antinuclear antibodies, and reduced saliva flow.

Conclusion: Our data indicate that Mer plays a protective role in SjS, similar to other autoimmune diseases. Furthermore, we suggest a series of events where enhanced ADAM17 activity increases Mer inactivation, depresses Mer signaling, and removes a protection against the loss of self-tolerance and onset of autoimmune disease in SjS^S mice.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/loss-of-tam-receptor-mer-contributes-to-sjogrens-syndrome-like-disease-in-mice/