Involvement of the interferon-gamma-induced T cell-attracting chemokines, interferon-gamma-inducible 10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the salivary gland lesions of patients with Sjögren's syndrome

Arthritis Rheum. 2002 Oct;46(10):2730-41. doi: 10.1002/art.10577.


Objective: To elucidate the mechanism of the development of T cell infiltrates in the salivary glands of patients with Sjögren's syndrome (SS), we studied T cell-attracting chemokines and their receptors.

Methods: The expression of the T cell-attracting chemokines, interferon-gamma (IFNgamma)-inducible 10-kd protein (IP-10; also called CXCL10), monokine induced by IFNgamma (Mig; also called CXCL9), and stromal cell-derived factor 1 (SDF-1; also called CXCL12), in salivary glands from SS patients was investigated by polymerase chain reaction-enzyme-linked immunosorbent assay (ELISA). Cells that produce chemokines and lymphocytes that express chemokine receptors were identified by immunohistochemistry. The production of IP-10 and Mig proteins by salivary epithelial cells in response to IFNgamma was determined by ELISA.

Results: Expression of IP-10 and Mig messenger RNA (mRNA) was significantly up-regulated in SS salivary glands compared with normal salivary glands (both P < 0.01). There was no significant difference in SDF-1 mRNA expression between the SS and normal salivary glands. IP-10 and Mig proteins were predominantly expressed in the ductal epithelium adjacent to lymphoid infiltrates. Most of the CD3+ infiltrating lymphocytes in dense periductal foci expressed CXCR3, the receptor for IP-10 and Mig. IFNgamma induced the production of high levels of IP-10 and Mig proteins from cultured SS salivary epithelial cells.

Conclusion: These findings suggest that IFNgamma stimulates the production of IP-10 and Mig in the SS ductal epithelium, and that IP-10 and Mig are involved in the accumulation of T cell infiltrates in the SS salivary gland. Chemokines or chemokine receptors could be a rational new therapeutic target in SS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cells, Cultured
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC / genetics*
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Interferon-gamma / pharmacology*
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • Receptors, CXCR3
  • Receptors, Chemokine / genetics
  • Salivary Ducts / cytology
  • Salivary Ducts / immunology
  • Salivary Glands / cytology
  • Salivary Glands / immunology*
  • Sjogren's Syndrome / immunology*
  • T-Lymphocytes / physiology*


  • CXCL9 protein, human
  • CXCR3 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Interferon-gamma