CCR4 versus CCR10 in human cutaneous TH lymphocyte trafficking

Dulce Soler, Tricia L. Humphreys, Stanley Spinola, James J. Campbell

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

The chemokine receptors (CCRs) CCR4 and CCR10, and the cutaneous lymphocyte antigen (CLA), have each been proposed as critical mediators of skin-specific TH lymphocyte homing in mice and humans. CLA initiates skin homing by mediating E-selectin-dependent tethering and rolling within cutaneous venules, but the specific roles of CCR4 and CCR10 are unclear. We have generated an antihuman CCR10 monoclonal antibody (mAb; 1B5) to illuminate the individual contributions of these molecules. This mAb allows us to compare CCR10, CCR4, and CLA expression within human TH populations. The mAb 1B5 recognizes functional CCR10 expression, as chemotactic responsiveness to cutaneous T-cell-attracting chemokine (CTACK)/CCL27 (a CCR10 ligand) parallels the staining of TH subsets. We find CCR10 expressed by only a minority (approximately 30%) of blood-borne, skin-homing (CLA+/CCR4+) TH cells. However, essentially all members of the relatively small "effector" (CLA+/CCR4+/CD27-/CCR7-) skin-homing TH population express CCR10. Most skin-infiltrating lymphocytes in allergic delayed-type hypersensitivity (DTH) and bacterial chancroid skin lesions express both CCR4 and CLA, but only about 10% express CCR10. This suggests for the 2 models of TH skin homing studied here that CCR10+ TH cells have no advantage over other CLA+/CCR4+ TH cells in homing to cutaneous sites. We conclude that the skin-homing TH compartment is itself divided into distinct subpopulations, the smaller of which expresses both CCR4 and CCR10, and the larger of which expresses only CCR4. Thus, CCR10 is unlikely to be necessary for cutaneous homing of TH cells in the models studied here. CCR10 may instead play a role in the movement of specialized "effector" cutaneous TH cells to and/or within epidermal microenvironments.

Original languageEnglish (US)
Pages (from-to)1677-1683
Number of pages7
JournalBlood
Volume101
Issue number5
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

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Lymphocytes
Skin
Antigens
Chemokine CCL27
E-Selectin
Chemokine Receptors
Blood
Monoclonal Antibodies
Chancroid
CD27 Antigens
Ligands
Molecules
Venules

ASJC Scopus subject areas

  • Hematology

Cite this

CCR4 versus CCR10 in human cutaneous TH lymphocyte trafficking. / Soler, Dulce; Humphreys, Tricia L.; Spinola, Stanley; Campbell, James J.

In: Blood, Vol. 101, No. 5, 01.03.2003, p. 1677-1683.

Research output: Contribution to journalArticle

Soler, D, Humphreys, TL, Spinola, S & Campbell, JJ 2003, 'CCR4 versus CCR10 in human cutaneous TH lymphocyte trafficking', Blood, vol. 101, no. 5, pp. 1677-1683. https://doi.org/10.1182/blood-2002-07-2348
Soler, Dulce ; Humphreys, Tricia L. ; Spinola, Stanley ; Campbell, James J. / CCR4 versus CCR10 in human cutaneous TH lymphocyte trafficking. In: Blood. 2003 ; Vol. 101, No. 5. pp. 1677-1683.
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abstract = "The chemokine receptors (CCRs) CCR4 and CCR10, and the cutaneous lymphocyte antigen (CLA), have each been proposed as critical mediators of skin-specific TH lymphocyte homing in mice and humans. CLA initiates skin homing by mediating E-selectin-dependent tethering and rolling within cutaneous venules, but the specific roles of CCR4 and CCR10 are unclear. We have generated an antihuman CCR10 monoclonal antibody (mAb; 1B5) to illuminate the individual contributions of these molecules. This mAb allows us to compare CCR10, CCR4, and CLA expression within human TH populations. The mAb 1B5 recognizes functional CCR10 expression, as chemotactic responsiveness to cutaneous T-cell-attracting chemokine (CTACK)/CCL27 (a CCR10 ligand) parallels the staining of TH subsets. We find CCR10 expressed by only a minority (approximately 30{\%}) of blood-borne, skin-homing (CLA+/CCR4+) TH cells. However, essentially all members of the relatively small {"}effector{"} (CLA+/CCR4+/CD27-/CCR7-) skin-homing TH population express CCR10. Most skin-infiltrating lymphocytes in allergic delayed-type hypersensitivity (DTH) and bacterial chancroid skin lesions express both CCR4 and CLA, but only about 10{\%} express CCR10. This suggests for the 2 models of TH skin homing studied here that CCR10+ TH cells have no advantage over other CLA+/CCR4+ TH cells in homing to cutaneous sites. We conclude that the skin-homing TH compartment is itself divided into distinct subpopulations, the smaller of which expresses both CCR4 and CCR10, and the larger of which expresses only CCR4. Thus, CCR10 is unlikely to be necessary for cutaneous homing of TH cells in the models studied here. CCR10 may instead play a role in the movement of specialized {"}effector{"} cutaneous TH cells to and/or within epidermal microenvironments.",
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