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Disruption of CXCR3 function impedes the development of Sjögren’s syndrome-like xerostomia in non-obese diabetic mice

The chemokine receptor CXCR3 plays an important role in T cell recruitment in various immune responses and autoimmune diseases. Expression of CXCR3 ligands, including CXCL9, CXCL10, and CXCL11, is elevated in the salivary glands of patients with Sjögren’s syndrome (SS). To elucidate whether interaction between CXCR3 and its ligands is required for the development of SS, we administrated an anti-CXCR3 blocking antibody (CXCR3-173) to the non-obese diabetic (NOD) mice, a well-defined model of SS, during the stage prior to disease onset. Treatment with this anti-CXCR3 antibody significantly improved salivary secretion, indicating a remission of SS clinical manifestation. Anti-CXCR3 treatment did not affect the gross leukocyte infiltration of the submandibular glands (SMGs) as assessed by hematoxylin and eosin staining. However, flow cytometric analysis showed that anti-CXCR3 treatment markedly reduced the percentage of CXCR3+CD8 T and CXCR3+CD44+CD8 T cells, without affecting that of CXCR3+CD4 T and CXCR3+CD44+CD4 T cells in the SMGs and submandibular lymph nodes, suggesting a preferential effect of this anti-CXCR3 treatment on CXCR3-expressing effector CD8 T cells. Meanwhile, SMG expression of inflammatory factor TNF-α was markedly diminished by anti-CXCR3 treatment. In accordance, anti-CXCR3 significantly enhanced SMG expression of tight junction protein claudin-1 and water channel protein aquaporin 5, two molecules that are crucial for normal salivary secretion and can be down-regulated by TNF-α. Taken together, these findings demonstrated that the interaction between the endogenous CXCR3 and its ligands plays a pro-inflammatory and pathogenic role in the development of SS-like xerostomia in the NOD mouse model.

Authors:   Jing Zhou; Qing Yu
Journal:   Laboratory Investigation
Year:   2018
Pages:   1
DOI:   10.1038/s41374-017-0013-4
Publication date:   18-Jan-2018
Facts, background information, dossiers
  • molecules
  • lymph nodes
  • hematoxylin
  • flow
  • cells
  • autoimmune diseases
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