title: Chemokine responses distinguish chemical-induced allergic from irritant skin inflammation: memory T cells make the difference.
abstract: BACKGROUND
  As clinical and histological features of allergic and irritant contact dermatitis share common characteristics, the differentiation between them in the preclinical and clinical evaluations of chemicals remains difficult.
  
  
  OBJECTIVE
  To identify the differences in the underlying immunological mechanisms of chemical-induced allergic or irritant skin responses.
  
  
  METHODS
  We systematically studied the involvement of chemokines in both diseases by quantitative real-time polymerase chain reaction in mice and humans. The cellular origin of relevant chemokines and receptors was determined using immunohistochemistry; functional relevance was demonstrated in vitro by transwell chemotaxis and in vivo by adoptive transfer experiments using a model of hapten-induced murine contact hypersensitivity.
  
  
  RESULTS
  Independent of overall skin inflammation, chemical-induced allergic and irritant skin responses showed distinct molecular expression profiles. In particular, chemokine genes predominantly regulated by T-cell effector cytokines demonstrated differential upregulation in hapten-specific skin inflammation. Notably, the expression of CXCR3 ligands, such as CXCL9 (Mig) and CXCL10 (IP-10), was upregulated in chemical-induced allergic skin responses when compared with irritant skin responses. Furthermore, we showed that inflammatory chemokines such as CXCL10 prime leukocytes to respond to CXCL12 (SDF-1), increasing their recruitment both in vitro and in vivo.
  
  
  CONCLUSIONS
  We provide important insights into the molecular basis of chemical-induced allergic and irritant contact dermatitis, identify novel markers suitable for their differentiation, and demonstrate the cooperation of inflammatory and homeostatic chemokines in the recruitment of pathogenic leukocyte subsets.
  
  
  CONCLUSIONS
  Molecular differences between both diseases represent the basis for new approaches to diagnostics and therapy.
authors.affiliation: Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Meller
authors.forename: Antti I
authors.initials: AI
authors.lastname: Lauerma
authors.forename: Frank Michael
authors.initials: FM
authors.lastname: Kopp
authors.forename: Franziska
authors.initials: F
authors.lastname: Winterberg
authors.forename: Minna
authors.initials: M
authors.lastname: Anthoni
authors.forename: Anja
authors.initials: A
authors.lastname: Müller
authors.forename: Michael
authors.initials: M
authors.lastname: Gombert
authors.forename: Anna
authors.initials: A
authors.lastname: Haahtela
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
authors.forename: Juliane
authors.initials: J
authors.lastname: Rieker
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Dieu-Nosjean
authors.forename: Robert Christof
authors.initials: RC
authors.lastname: Kubitza
authors.forename: Ernst
authors.initials: E
authors.lastname: Gleichmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D017449:Dermatitis, Allergic Contact / Q000175:diagnosis* / Q000276:immunology* / Q000473:pathology; D017453:Dermatitis, Irritant / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018925:Chemokines