Submitted December 18, 2007
Accepted August 26, 2008
Anti-inflammatory effects of an inflammatory chemokine: CCL2 inhibits lymphocyte homing by modulation of CCL21 triggered integrin-mediated adhesions
Liat Flaishon, Gili Hart, Einat Zelman, Christine Moussion, Valentin Grabovsky, Guy Lapidot Tal, Sara Feigelson, Raanan Margalit, Alon Harmelin, Tamar Avin- Wittenberg, David Shoseyov, Ronen Alon, Jean-Philippe Girard, and Idit Shachar*
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
Laboratory of Vascular Biology, IPBS CNRS UMR 5089, Toulouse, France
Experimental Animal Center, Weizmann Institute of Science, Rehovot, Israel
Department of Pediatrics, Hadassah Mount Scopus Hospital, Jerusalem, Israel
* Corresponding author; email: idit.shachar{at}weizmann.ac.il.
Our studies focus on the pathways that restrict homing of specific subsets of immune cells, and thereby fine tune the immune response at specific lymphoid and peripheral tissues. Here, we report that CCL2 (at picomolar (pM) levels) renders both murine and human T cells defective in their ability to develop CCR7 triggered activation of LFA-1 and LFA-1-mediated adhesion strengthening to endothelial ICAM-1 both in vitro and in vivo. CCL2 also attenuated lymphocyte chemotaxis towards lymph node chemokines. Consequently, low dose CCL2 inhibited lymphocyte homing to peripheral lymph nodes but did not affect lymphocyte trafficking through the spleen. Impaired homing of lymphocytes to peripheral lymph nodes resulted in attenuated progression of both asthma and adjuvant-arthritis. Thus, pM levels of circulating CCL2 can exert global suppressive effects on T cell trafficking and differentiation within peripheral lymph nodes, and may be clinically beneficial as an anti-inflammatory agent.
