CTACK, a skin-associated chemokine that preferentially attracts skin-homing memory T cells

Morales, Janine; Homey, Bernhard; Vicari, Alain; Hudak, Susan; Oldham, Elizabeth R.; Hedrick, Joseph A.; Orozco, Rocio; Copeland, Neal G.; Jenkins, Nancy A.; McEvoy, Leslie M.; Zlotnik, Albert

doi:10.1073/pnas.96.25.14470

Cited by 468 publications

(403 citation statements)

References 31 publications

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“…A recent report concluded that the only CCL27-responsive cells in human peripheral blood were CLA ϩ memory CD4 and CD8 T cells (9). These CCR10 Abs were used in conjunction with lineage-specific Abs to investigate CCR10 expression by different blood-derived cells to confirm and extend this observation.…”

Section: Resultsmentioning

confidence: 97%

“…Therefore, it was postulated that a skin-specific activation cue (step 2) or chemoattractant (step 4) might confer skin-specific homing to the CLA ϩ T cell population or to a subset of cells within this population. CCL27 is the only skin-specific chemokine known (9) and by interacting with CLA ϩ /CCR10 ϩ memory T cells, it may provide the postulated skin-specific step that facilitates these cells' entry into cutaneous sites.…”

Section: Discussionmentioning

confidence: 99%

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Immune Surveillance and Effector Functions of CCR10+ Skin Homing T Cells

Hudak¹,

Hagen²,

Liu³

et al. 2002

The Journal of Immunology

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108

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Skin homing T cells carry memory for cutaneous Ags and play an important sentinel and effector role in host defense against pathogens that enter via the skin. CCR10 is a chemokine receptor that is preferentially expressed among blood leukocytes by a subset of memory CD4 and CD8 T cells that coexpress the skin-homing receptor cutaneous lymphocyte Ag (CLA), but not the gut-homing receptor α4β7. Homing and chemokine receptor coexpression studies detailed in this study suggest that the CLA+/CCR10+ memory CD4 T cell population contains members that have access to both secondary lymphoid organ and skin compartments; and therefore, can act as both “central” and “effector” memory T cells. Consistent with this effector phenotype, CLA+/CCR10+ memory CD4 T cells from normal donors secrete TNF and IFN-γ but minimal IL-4 and IL-10 following in vitro stimulation. Interactions of CCR10 and its skin-associated ligand CC ligand 27 may play an important role in facilitating memory T cell entry into cutaneous sites during times of inflammation.

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Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Immune Surveillance and Effector Functions of CCR10+ Skin Homing T Cells

Hudak¹,

Hagen²,

Liu³

et al. 2002

The Journal of Immunology

Self Cite

108

View full text Add to dashboard Cite

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“…As discussed above, gene targeting has also revealed unequivocally a role for CCR6 in the regulation of DC traffic in the mucosal compartment. CCL17/TARC and CCL27/CTAK are important for the traffic of skin homing T lymphocytes (55,56). CCL17/TARC recruits CLA + T cells, which are the predominant type present in the skin.…”

Section: Polarized Responsesmentioning

confidence: 99%

The chemokine system: tuning and shaping by regulation of receptor expression and coupling in polarized responses

Locati

Otero

Schioppa

et al. 2002

Allergy

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“…Constitutively expressed chemokines act in primary and secondary lymphoid organs [16,17,26] and peripheral tissues [27,28]. The CCR7 ligands, CCL19 and CCL21 [29,30], are expressed in the T-cell area of secondary lymphoid organs as well as on high endothelial venules (HEV) [31] and orchestrate the migration of CCR7 1 cells.…”

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confidence: 99%

Synergy‐inducing chemokines enhance CCR2 ligand activities on monocytes

Kuscher¹,

Danelon²,

Paoletti³

et al. 2009

Eur J Immunol

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The migration of monocytes to sites of inflammation is largely determined by their response to chemokines. Although the chemokine specificities and expression patterns of chemokine receptors are well defined, it is still a matter of debate how cells integrate the messages provided by different chemokines that are concomitantly produced in physiological or pathological situations in vivo. We present evidence for one regulatory mechanism of human monocyte trafficking. Monocytes can integrate stimuli provided by inflammatory chemokines in the presence of homeostatic chemokines. In particular, migration and cell responses could occur at much lower concentrations of the CCR2 agonists, in the presence of chemokines (CCL19 and CCL21) that per se do not act on monocytes. Binding studies on CCR2 1 cells showed that CCL19 and CCL21 do not compete with the CCR2 agonist CCL2. Furthermore, the presence of CCL19 or CCL21 could influence the degradation of CCL2 and CCL7 on cells expressing the decoy receptor D6. These findings disclose a new scenario to further comprehend the complexity of chemokinebased monocyte trafficking in a vast variety of human inflammatory disorders.Key words: Chemokine receptors . Chemokines . Monocytes . Synergism IntroductionConcomitant exposure to multiple chemokines, the key controllers of several immune cell functions [1], can result in enhancement of immune responses. Only recently, a broad phenomenon known as ''chemokine synergism'' has been identified [2][3][4][5][6][7][8][9][10]. Cells expressing two or more chemokine receptors, in the presence of the selective agonists, can amplify their response [2][3][4][5][6]11]. The responses mediated by low agonist concentrations can be powerfully enhanced by non-ligand chemokines in cells that do not bear the second chemokine receptor [7][8][9]. Using different biochemical approaches, these studies demonstrated that CC and CXC chemokines form heteromeric complexes, which could endow the agonist with higher activity [7,9,12].Chemokines mediate their effects through interactions with heterotrimeric G-protein-coupled receptors [13][14][15]. Most leukocytes express more than one chemokine receptor and, hence, can respond to more than one chemokine. Additionally, a great variety of in situ experiments demonstrated the concomitant expression of chemokines at target sites of leukocyte trafficking and homing [16][17][18][19][20][21].Many chemokines, apart from being agonistic for their receptors, were shown to act as natural antagonists on one or several receptors in vitro and in vivo [22]. Naturally occurring N-terminal truncations of chemokines have been identified in vivo [23] and numerous enzymes were shown to generate truncations of chemokines that render them less active or inactive [24,25]. Therefore, there are strong indications that a cell needs to 1118integrate more than one signal provided by its environment and that environmental factors other than agonists might influence their responses.Chemokine production can be either constitutive or triggere...

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CTACK, a skin-associated chemokine that preferentially attracts skin-homing memory T cells

Cited by 468 publications

References 31 publications

Immune Surveillance and Effector Functions of CCR10+ Skin Homing T Cells

Immune Surveillance and Effector Functions of CCR10+ Skin Homing T Cells

The chemokine system: tuning and shaping by regulation of receptor expression and coupling in polarized responses

Synergy‐inducing chemokines enhance CCR2 ligand activities on monocytes

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