Nonredundant role of CCRL2 in lung dendritic cell trafficking.
Chemokine CC motif receptor-like 2 (CCRL2) is a heptahelic transmembrane receptor that shows the highest degree of homology with CCR1, an inflammatory chemokine receptor. CCRL2 mRNA was rapidly (30 minutes) and transiently (2-4 hours) regulated during dendritic cell (DC) maturation. Protein expression paralleled RNA regulation. In vivo, CCRL2 was expressed by activated DC and macrophages, but not by eosinophils and T cells. CCRL2(-/-) mice showed normal recruitment of circulating DC into the lung, but a defective trafficking of antigen-loaded lung DC to mediastinal lymph nodes. This defect was associated to a reduction in lymph node cellularity and reduced priming of T helper cell 2 response. CCRL2(-/-) mice were protected in a model of ovalbumin-induced airway inflammation, with reduced leukocyte recruitment in the BAL (eosinophils and mononuclear cells) and reduced production of the T helper cell 2 cytokines, interleukin-4 and -5, and chemokines CCL11 and CCL17. The central role of CCRL2 deficiency in DC was supported by the fact that adoptive transfer of CCRL2(-/-) antigen-loaded DC in wild-type animals recapitulated the phenotype observed in knockout mice. These data show a nonredundant role of CCRL2 in lung DC trafficking and propose a role for this receptor in the control of excessive airway inflammatory responses.
Otero
Karel
K
Istituto Clinico Humanitas, IRCCS, Rozzano, Italy.
Vecchi
Annunciata
A
Hirsch
Emilio
E
Kearley
Jennifer
J
Vermi
William
W
Del Prete
Annalisa
A
Gonzalvo-Feo
Safiyè
S
Garlanda
Cecilia
C
Azzolino
Ornella
O
Salogni
Laura
L
Lloyd
Clare M
CM
Facchetti
Fabio
F
Mantovani
Alberto
A
Sozzani
Silvano
S
D000485:Allergens / Q000276:immunology; D000818:Animals; D002465:Cell Movement; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007249:Inflammation / Q000139:chemically induced; D008168:Lung / Q000166:cytology*; D008198:Lymph Nodes / Q000166:cytology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*
D000485:Allergens; C111851:Ccrl2 protein, mouse; D016207:Cytokines; D054388:Receptors, CCR; D019707:Receptors, Chemokine