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, Idit Shachar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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-1mediated adhesion strengthening to endothelial ICAM-1 both in vitro and in vivo. CCL2 also attenuated lymphocyte chemotaxis toward lymph node chemo-kines. 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.

Original languageAmerican English
Pages (from-to)5016-5025
Number of pages10
JournalBlood
Volume112
Issue number13
DOIs
StatePublished - 15 Dec 2008
Externally publishedYes

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