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T
Cell Attractant Chemokine Expression Initiates Lacrimal Gland Destruction
in Nonobese Diabetic Mice |
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Jyrki Törnwall,
Thomas E. Lane, Robert I. Fox, and Howard S. Fox |
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Department
of Neuropharmacology (JT, TEL, HSF), The Scripps Research Institute, La
Jolla, California; Departments of Oral and Maxillofacial Surgery (JT), Institute
of Dentistry and Helsinki University Central Hospital, Helsinki, Finland;
and The Scripps Clinic and Research Foundation (RIF), La Jolla, California |
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SUMMARY: By inducing both
adhesion and migration of lymphocytes, chemokines play an important role
in immune and inflammatory responses. To learn how these processes promote
disease, we have examined the activities of chemokines in the lacrimal glands
(LG) of nonobese diabetic (NOD) mice, an animal model of Sjogren's syndrome
(SS). The expression of three molecules in the chemokine superfamily, RANTES,
IP-10 and lymphotactin, correlated with the local recruitment of lymphocytes
into the LG of NOD mice. Both RANTES and IP-10 gene transcripts were first
detected in these LG when the mice were 8 weeks of age and amounts increased
markedly during the course of active disease; lymphotactin mRNA was also
expressed but at lower levels. In situ hybridization of LG indicated that
lymphocytic cells in the inflammatory infiltrates were responsible for the
production of RANTES and IP-10. Concomitant with the induction of chemokine
expression was the appearance of cellular receptors for RANTES (CCR1, CCR5)
and IP-10 (CXCR3). Furthermore, anti-RANTES treatment significantly reduced
inflammation in the LG from NOD mice. In the SS-like disease of NOD mice,
this distinct pattern of activity provides evidence for the contribution
of these components to site- and time-specific recruitment of lymphocytes
in the characteristic destruction of glandular structures. |
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