title: Mouse CCL8, a CCR8 agonist, promotes atopic dermatitis by recruiting IL-5+ T(H)2 cells.
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.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Islam
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Chang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Colvin
authors.forename: Mike H
authors.initials: MH
authors.lastname: Byrne
authors.forename: Michelle L
authors.initials: ML
authors.lastname: McCully
authors.forename: Bernhard
authors.initials: B
authors.lastname: Moser
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Lira
authors.forename: Israel F
authors.initials: IF
authors.lastname: Charo
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D020013:Calcium Signaling / Q000276:immunology; D002478:Cells, Cultured; D054402:Chemokine CCL1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054412:Chemokine CCL8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology; D003001:Cloning, Molecular; D003876:Dermatitis, Atopic / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D012867:Skin / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: C502258:Ccl1 protein, mouse; D054402:Chemokine CCL1; D054412:Chemokine CCL8; D015848:Interleukin-5; D016201:Receptors, Lymphocyte Homing