Sjögren's syndrome and chemokines.

Abstract

Interferon (IFN)-γ-induced protein 10 (IP-10) and its receptor, chemokine (C-X-C motif) receptor (CXCR)3, appear to contribute to the pathogenesis of Sjögren's syndrome (SS). The expression of IP-10 and CXCR3 is increased, in salivary glands from SS patients, both in the ductal epithelium adjacent to lymphoid infiltrates and in lymphocytes. IFN-γ induces the production of high levels of IP-10 and monokine induced by IFN-γ (MIG) proteins from cultured SS salivary epithelial cells. Under the influence of IFN-γ, IP-10 secreted by salivary cells, recruits T helper (Th)1 lymphocytes that may be responsible for enhanced IFN-γ, which in turn stimulates a further IP-10 secretion from epithelial cells creating an amplification feedback loop and perpetuating the autoimmune process. Determination of high level of IP-10 in tears and saliva is therefore a marker of a Th1 orientated immune response. In experimental settings IP-10 antagonists can ameliorate the progression of autoimmune sialadenitis, providing a new therapeutic approach to SS. Further studies are needed to investigate whether IP-10 is a novel therapeutic target in SS in humans.