title: Anti-inflammatory effects of an inflammatory chemokine: CCL2 inhibits lymphocyte homing by modulation of CCL21-triggered integrin-mediated adhesions.
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-1-mediated adhesion strengthening to endothelial ICAM-1 both in vitro and in vivo. CCL2 also attenuated lymphocyte chemotaxis toward 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.
authors.affiliation: Department of Immunology, the Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Flaishon
authors.forename: Gili
authors.initials: G
authors.lastname: Hart
authors.forename: Einat
authors.initials: E
authors.lastname: Zelman
authors.forename: Christine
authors.initials: C
authors.lastname: Moussion
authors.forename: Valentin
authors.initials: V
authors.lastname: Grabovsky
authors.forename: Guy
authors.initials: G
authors.lastname: Lapidot Tal
authors.forename: Sara
authors.initials: S
authors.lastname: Feigelson
authors.forename: Raanan
authors.initials: R
authors.lastname: Margalit
authors.forename: Alon
authors.initials: A
authors.lastname: Harmelin
authors.forename: Tamar
authors.initials: T
authors.lastname: Avin-Wittenberg
authors.forename: David
authors.initials: D
authors.lastname: Shoseyov
authors.forename: Ronen
authors.initials: R
authors.lastname: Alon
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Girard
authors.forename: Idit
authors.initials: I
authors.lastname: Shachar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001168:Arthritis / Q000517:prevention & control; D001249:Asthma / Q000517:prevention & control; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000494:pharmacology*; D054421:Chemokine CCL21 / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006801:Humans; D007109:Immunity; D016023:Integrins / Q000378:metabolism*; D008198:Lymph Nodes; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D054400:Receptors, CCR7 / Q000378:metabolism; D013154:Spleen
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D054421:Chemokine CCL21; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D054400:Receptors, CCR7