Mouse CCL8, a CCR8 Agonist, Promotes Atopic Dermatitis by Recruiting IL-5+ T(H)2 Cells

Overview

Journal Nat Immunol

Date 2011 Jan 11

PMID 21217759

Citations 148

Authors

Sabina A Islam

Daniel S Chang

Richard A Colvin

Mike H Byrne

Michelle L McCully

Bernhard Moser

Sergio A Lira

Israel F Charo

Andrew D Luster

Affiliations

Soon will be listed here.

Abstract

Mouse CCL8 is a CC chemokine of the monocyte chemoattractant protein (MCP) family whose biological activity and receptor usage have remained elusive. Here we show that CCL8 is highly expressed in the skin, where it serves as an agonist for the chemokine receptor CCR8 but not for CCR2. This distinguishes CCL8 from all other MCP chemokines. CCL8 responsiveness defined a population of highly differentiated, CCR8-expressing inflammatory T helper type 2 (T(H)2) cells enriched for interleukin (IL)-5. Ccr8- and Ccl8-deficient mice had markedly less eosinophilic inflammation than wild-type or Ccr4-deficient mice in a model of chronic atopic dermatitis. Adoptive transfer studies established CCR8 as a key regulator of T(H)2 cell recruitment into allergen-inflamed skin. In humans, CCR8 expression also defined an IL-5-enriched T(H)2 cell subset. The CCL8-CCR8 chemokine axis is therefore a crucial regulator of T(H)2 cell homing that drives IL-5-mediated chronic allergic inflammation.

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