Identification of CCR8: A Human Monocyte and Thymus Receptor for the CC Chemokine I-309

Abstract

The human CC chemokine I-309 is a potent monocyte chemoattractant and inhibits apoptosis in thymic cell lines. Here, we identify a specific human I-309 receptor, and name it CCR8 according to an accepted nomenclature system. The receptor has seven predicted transmembrane domains, is expressed constitutively in monocytes and thymus, and is encoded by a previously reported gene of previously unknown function named, alternatively, CY6, TER1, and CKR-L1. After transfection with the CY6 open reading frame, a mouse pre–B cell line exhibited calcium flux and chemotaxis in response to I-309 (EC50 = 2 nM for each), whereas 20 other chemokines were inactive. Signaling was sensitive to pertussis toxin, suggesting coupling to a Gi-type G protein. These properties parallel those of endogenous I-309 receptors expressed in an HL-60 clone 15 cell line model. The apparent monogamous relationship between I-309 and CCR8 is unusual among known CC chemokines and known CC chemokine receptors. CCR8 may regulate monocyte chemotaxis and thymic cell line apoptosis.

Chemokines: signal lamps for trafficking of T and B cells for development and effector function

“…CCR8, a receptor for I-309, TARC and MIP-1␤, is expressed in IL-2-activated T cells, but not in naive/resting cells [79]. a CCR8 is also expressed in thymus [111], and may mediate chemotaxis of some thymocyte subsets to MIP-1␤. The underlined chemokine receptors are characteristics of Th1 or Th2 cells.…”

Chemokines in tumor angiogenesis and metastasis

“…CCR6 has been shown to be a receptor for CCL20 [62]. CCL19 and CCL21 bind to CCR7 [63] while CCR8 appears to bind CCL1 specifically [64]. CCR9 is a receptor for CCL25 [65].…”

Absence of CCR8 Does Not Impair the Response to Ovalbumin-Induced Allergic Airway Disease

“…3C). In addition, sections were prepared from lungs of animals sacrificed on days [15][16][17][18][19], and stained to analyze the tissue infiltrates. Increasing perivascular and peribronchial infiltrates were observed throughout treatment, with predominant increases in eosinophils (Fig.…”

“…CCR8 is the receptor for C-C chemokine ligand (CCL) 3 1 (human I-309, murine T cell-activated gene 3 (TCA3)) (15)(16)(17)(18). Expression of the CCR8 message is maximal in the thymus (15, 18 -20), in which the CCR8 protein shows finely regulated expression that increases throughout differentiation of the CD4 ϩ lineage (21).…”