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

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Abstract
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‐γ (IFNγ)–inducible 10‐kd protein (IP‐10; also called CXCL10), monokine induced by IFNγ (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 IFNγ 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. IFNγ induced the production of high levels of IP‐10 and Mig proteins from cultured SS salivary epithelial cells. Conclusion These findings suggest that IFNγ 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.