title: Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)(+) TH2/TH1 cell imbalance, whereas adults acquire CLA(+) TH22/TC22 cell subsets.
abstract: BACKGROUND
  Identifying differences and similarities between cutaneous lymphocyte antigen (CLA)(+) polarized T-cell subsets in children versus adults with atopic dermatitis (AD) is critical for directing new treatments toward children.
  
  
  OBJECTIVE
  We sought to compare activation markers and frequencies of skin-homing (CLA(+)) versus systemic (CLA(-)) "polar" CD4 and CD8 T-cell subsets in patients with early pediatric AD, adults with AD, and control subjects.
  
  
  METHODS
  Flow cytometry was used to measure CD69/inducible costimulator/HLA-DR frequency in memory cell subsets, as well as IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines, defining TH1/cytotoxic T (TC) 1, TH2/TC2, TH9/TC9, TH17/TC17, and TH22/TC22 populations in CD4 and CD8 cells, respectively. We compared peripheral blood from 19 children less than 5 years old and 42 adults with well-characterized moderate-to-severe AD, as well as age-matched control subjects (17 children and 25 adults).
  
  
  RESULTS
  Selective inducible costimulator activation (P < .001) was seen in children. CLA(+) TH2 T cells were markedly expanded in both children and adults with AD compared with those in control subjects, but decreases in CLA(+) TH1 T-cell numbers were greater in children with AD (17% vs 7.4%, P = .007). Unlike in adults, no imbalances were detected in CLA(-) T cells from pediatric patients with AD nor were there altered frequencies of TH22 T cells within the CLA(+) or CLA(-) compartments. Adults with AD had increased frequencies of IL-22-producing CD4 and CD8 T cells within the skin-homing population, compared with controls (9.5% vs 4.5% and 8.6% vs 2.4%, respectively; P < .001), as well as increased HLA-DR activation (P < .01).
  
  
  CONCLUSIONS
  These data suggest that TH2 activation within skin-homing T cells might drive AD in children and that reduced counterregulation by TH1 T cells might contribute to excess TH2 activation. TH22 "spreading" of AD is not seen in young children and might be influenced by immune development, disease chronicity, or recurrent skin infections.
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Tali
authors.initials: T
authors.lastname: Czarnowicki
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Hitokazu
authors.initials: H
authors.lastname: Esaki
authors.affiliation: Translational Technology Core Laboratory, Rockefeller University, New York, NY.
authors.forename: Juana
authors.initials: J
authors.lastname: Gonzalez
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Dana
authors.initials: D
authors.lastname: Malajian
authors.affiliation: Department of Dermatology, Tel-Hashomer Hospital, Tel Aviv, Israel.
authors.forename: Avner
authors.initials: A
authors.lastname: Shemer
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Shinji
authors.initials: S
authors.lastname: Noda
authors.affiliation: Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Sreya
authors.initials: S
authors.lastname: Talasila
authors.affiliation: Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Adam
authors.initials: A
authors.lastname: Berry
authors.affiliation: Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Jayla
authors.initials: J
authors.lastname: Gray
authors.affiliation: Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Lauren
authors.initials: L
authors.lastname: Becker
authors.affiliation: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Yeriel
authors.initials: Y
authors.lastname: Estrada
authors.affiliation: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Xiuzhong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Paller
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: Emma.Guttman@mountsinai.org.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007378:Interleukins / Q000378:metabolism*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D058408:Th1-Th2 Balance; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D007378:Interleukins; D008562:Membrane Glycoproteins; D000097043:Interleukin-22; C063419:CTAGE1 protein, human
keywords: Atopic dermatitis; CD69; HLA-DR; IFN-γ; IL-13; IL-22; T cell; cutaneous lymphocyte antigen; inducible costimulator