RGD Reference Report - CC chemokine receptor (CCR)2 is required for langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells. Absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, b cell outgrowth, and sustained neutrophilic inflammation. - Rat Genome Database

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CC chemokine receptor (CCR)2 is required for langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells. Absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, b cell outgrowth, and sustained neutrophilic inflammation.

Authors: Sato, N  Ahuja, SK  Quinones, M  Kostecki, V  Reddick, RL  Melby, PC  Kuziel, WA  Ahuja, SS 
Citation: Sato N, etal., J Exp Med. 2000 Jul 17;192(2):205-18.
RGD ID: 8661227
Pubmed: PMID:10899907   (View Abstract at PubMed)
PMCID: PMC2193245   (View Article at PubMed Central)

There is growing evidence that chemokines and their receptors regulate the movement and interaction of antigen-presenting cells such as dendritic cells (DCs) and T cells. We tested the hypothesis that the CC chemokine receptor (CCR)2 and CCR5 and the chemokine macrophage inflammatory protein (MIP)-1alpha, a ligand for CCR5, influence DC migration and localization. We found that deficiency of CCR2 but not CCR5 or MIP-1alpha led to distinct defects in DC biology. Langerhans cell (skin DC) density in CCR2-null mice was normal, and their ability to migrate into the dermis was intact; however, their migration to the draining lymph nodes was markedly impaired. CCR2-null mice had lower numbers of DCs in the spleen, and this was primarily due to a reduction in the CD8alpha(1) T helper cell type 1 (Th1)-inducing subset of DCs. Additionally, there was a block in the Leishmania major infection-induced relocalization of splenic DCs from the marginal zone to the T cell areas. We propose that these DC defects, in conjunction with increased expression of B lymphocyte chemoattractant, a B cell-specific chemokine, may collectively contribute to the striking B cell outgrowth and Th2 cytokine-biased nonhealing phenotype that we observed in CCR2-deficient mice infected with L. major. This disease phenotype in mice with an L. major-resistant genetic background but lacking CCR2 is strikingly reminiscent of that observed typically in mice with an L. major-susceptible genetic background. Thus, CCR2 is an important determinant of not only DC migration and localization but also the development of protective cell-mediated immune responses to L. major.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CCR2Humanallergic contact dermatitis  ISOCcr2 (Mus musculus) RGD 
Ccr2Ratallergic contact dermatitis  ISOCcr2 (Mus musculus) RGD 
Ccr2Mouseallergic contact dermatitis  IMP  RGD 
CCR2Humanleishmaniasis  ISOCcr2 (Mus musculus) RGD 
Ccr2Ratleishmaniasis  ISOCcr2 (Mus musculus) RGD 
Ccr2Mouseleishmaniasis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Mus musculus)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Homo sapiens)
CCR2  (C-C motif chemokine receptor 2)


Additional Information