Dhavalkumar D. Patel, M.D. Ph.D.
Professor of Medicine and Microbiology and Immunology
Director, Thurston Arthritis Research Center
Chief, Division of Rheumatology, Allergy and Immunology

Chemokines and their receptors are intimately involved in regulating organ-specific leukocyte trafficking and inflammation. We have been studying the roles that chemokines and their G-protein coupled receptors (GPCRs) play in leukocyte trafficking from the blood into tissues. Recently, we and others have identified that the chemokine fractalkine (FKN, CX3CL1), with its receptor (CX3CR1), is critically involved in atherosclerosis, cardiac transplant rejection and tumor surveillance. In addition to the chemotactic and other functional properties attributed to chemokines, we have shown that FKN and CX3CR1 have remarkable cell adhesion properties that may contribute to cell migration and function. It has been shown in vitro that these cell adhesion properties promote conjugate formation between effector cells such as NK cells and their targets to enhance killing of targets. We are testing the hypothesis that FKN and CX3CR1 regulate the host immune response by affecting effector cell trafficking and function. We are also studying the basic mechanisms of chemotaxis focusing on the _-arrestin - G receptor kinase (GRK) system. Using knockout mice, we have shown that _-arrestin-2 and GRK6 are critical regulators of chemotaxis with pleotropic roles depending on the receptors being activated. Our studies and those of collaborators are showing that mice deficient in specific components of the _arrestin-GRK system have markedly altered inflammatory responses. We are dissecting the mechanisms by which _-arrestin2 and GRKs regulate leukocyte trafficking to sites of inflammation.
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Publications:
Kader, H.A., Tchernev, V.T., Satyaraj, E., Lejnine, S., Kotler, G., Kingsmore, S.F. and D.D. Patel. 2005. Protein Microarray Analysis of Disease Activity in Pediatric Inflammatory Bowel Disease Demonstrates Elevated Serum PLGF, IL-7, TGF-b1 and IL-12p40 Levels in Crohn’s Disease and Ulcerative Colitis Patients in Remission versus Active Disease. Am. J. Gastroenterol. 100:414-423.

Kavelaars, A., Vroon, A., Raatgever, R., Fong, A.M., Premont, R., Patel, D.D., Lefkowitz, R. and C.J. Heijnen. 2003. Increased acute inflammation, Leukotriene B4-induced chemotaxis and signaling in mice deficient for GRK6. J. Immunol. 171:6128-6134.

Walker, J.K.L., Fong, A.M., Lawson, B.L., Savov, J.D., Patel, D.D., Schwartz, D.A., and R.J. Lefkowitz. 2003. Beta-arrestin-2 regulates the development of allergic asthma. J. Clin. Invest. 112:566-574.

Fong, A.M., Premont, R., Richardson, R.M., Yu, A.M., Lefkowitz, R.J., and D.D. Patel. 2002. Defective lymphocyte chemotaxis in b-arrestin2- and GRK6-deficient mice. Proc. Natl. Acad. Sci. 99:7478-7483.

Fong, A.M., Robinson, L.A., Steeber, D.A., Tedder, T.F., Yoshie, O., Imai, T. and D.D. Patel. 1998. Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion and activation under physiologic flow. J. Exp. Med. 188:1413-1419.