Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing T-cell population
Past studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed before the identification of TH9, TH17, and TH22 T-cell populations in human subjects. We sought to quantify TH1, TH2, TH9, TH17, and TH22 T-cell populations...
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| Published in | Journal of allergy and clinical immunology Vol. 136; no. 1; pp. 104 - 115.e7 |
|---|---|
| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.07.2015
Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Past studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed before the identification of TH9, TH17, and TH22 T-cell populations in human subjects.
We sought to quantify TH1, TH2, TH9, TH17, and TH22 T-cell populations and corresponding CD8+ T-cell subsets in both cutaneous lymphocyte antigen (CLA)–positive and CLA− T-cell subsets in patients with AD and control subjects.
We studied 42 adults with severe AD (mean SCORAD score, 65) and 25 healthy subjects using an 11-color flow cytometric antibody panel. Frequencies of IFN-γ–, IL-22–, IL-13–, IL-17–, and IL-9–producing CD4+ and CD8+ T cells were compared in CLA− and CLA+ populations.
We measured increased TH2/TC2/IL-13+ and TH22/TC22/IL-22+ populations (P < .1) in patients with severe AD versus control subjects, with significant differences in CLA+ T-cell numbers (P < .01). A significantly lower frequency of CLA+ IFN-γ–producing cells was observed in patients with AD, with no significant differences in CLA− T-cell numbers. The CLA+ TH1/TH2 and TC1/TC2 ratio was highly imbalanced in patients with AD (10 vs 3 [P = .005] and 19 vs 7 [P < .001], respectively). Positive correlations were found between frequencies of IL-13– and IL-22–producing CD4+ and CD8+ T cells (r = 0.5 and 0.8, respectively; P < .0001), and frequencies of IL-13–producing CLA+ cells were also correlated with IgE levels and SCORAD scores. Patients with AD with skin infections had higher CD4+ IL-22+ and IL-17+ cell frequencies, which were highly significant among CLA− cells (IL-22: 3.7 vs 1.7 [P < .001] and IL-17: 1.7 vs 0.6 [P < .001]), with less significant effects among CLA+ T cells (IL-22: 11 vs 7.5, P = .04).
Severe AD is accompanied by expansion of skin-homing TH2/TC2 and TH22/TC22 subsets with lower TH1/TC1 frequencies. These data create a critical basis for studying alterations in immune activation in adults and pediatric patients with AD. |
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| AbstractList | Background Past studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed before the identification of TH9, TH17, and TH22 T-cell populations in human subjects. Objective We sought to quantify TH1, TH2, TH9, TH17, and TH22 T-cell populations and corresponding CD8+ T-cell subsets in both cutaneous lymphocyte antigen (CLA)-positive and CLA- T-cell subsets in patients with AD and control subjects. Methods We studied 42 adults with severe AD (mean SCORAD score, 65) and 25 healthy subjects using an 11-color flow cytometric antibody panel. Frequencies of IFN- gamma -, IL-22-, IL-13-, IL-17-, and IL-9-producing CD4+ and CD8+ T cells were compared in CLA- and CLA+ populations. Results We measured increased TH2/TC2/IL-13+ and TH22/TC22/IL-22+ populations (P < .1) in patients with severe AD versus control subjects, with significant differences in CLA+ T-cell numbers (P < .01). A significantly lower frequency of CLA+ IFN- gamma -producing cells was observed in patients with AD, with no significant differences in CLA- T-cell numbers. The CLA+ TH1/TH2 and TC1/TC2 ratio was highly imbalanced in patients with AD (10 vs 3 [P = .005] and 19 vs 7 [P < .001], respectively). Positive correlations were found between frequencies of IL-13- and IL-22-producing CD4+ and CD8+ T cells (r = 0.5 and 0.8, respectively; P < .0001), and frequencies of IL-13-producing CLA+ cells were also correlated with IgE levels and SCORAD scores. Patients with AD with skin infections had higher CD4+ IL-22+ and IL-17+ cell frequencies, which were highly significant among CLA- cells (IL-22: 3.7 vs 1.7 [P < .001] and IL-17: 1.7 vs 0.6 [P < .001]), with less significant effects among CLA+ T cells (IL-22: 11 vs 7.5, P = .04). Conclusions Severe AD is accompanied by expansion of skin-homing TH2/TC2 and TH22/TC22 subsets with lower TH1/TC1 frequencies. These data create a critical basis for studying alterations in immune activation in adults and pediatric patients with AD. Past studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed before the identification of TH9, TH17, and TH22 T-cell populations in human subjects. We sought to quantify TH1, TH2, TH9, TH17, and TH22 T-cell populations and corresponding CD8+ T-cell subsets in both cutaneous lymphocyte antigen (CLA)–positive and CLA− T-cell subsets in patients with AD and control subjects. We studied 42 adults with severe AD (mean SCORAD score, 65) and 25 healthy subjects using an 11-color flow cytometric antibody panel. Frequencies of IFN-γ–, IL-22–, IL-13–, IL-17–, and IL-9–producing CD4+ and CD8+ T cells were compared in CLA− and CLA+ populations. We measured increased TH2/TC2/IL-13+ and TH22/TC22/IL-22+ populations (P < .1) in patients with severe AD versus control subjects, with significant differences in CLA+ T-cell numbers (P < .01). A significantly lower frequency of CLA+ IFN-γ–producing cells was observed in patients with AD, with no significant differences in CLA− T-cell numbers. The CLA+ TH1/TH2 and TC1/TC2 ratio was highly imbalanced in patients with AD (10 vs 3 [P = .005] and 19 vs 7 [P < .001], respectively). Positive correlations were found between frequencies of IL-13– and IL-22–producing CD4+ and CD8+ T cells (r = 0.5 and 0.8, respectively; P < .0001), and frequencies of IL-13–producing CLA+ cells were also correlated with IgE levels and SCORAD scores. Patients with AD with skin infections had higher CD4+ IL-22+ and IL-17+ cell frequencies, which were highly significant among CLA− cells (IL-22: 3.7 vs 1.7 [P < .001] and IL-17: 1.7 vs 0.6 [P < .001]), with less significant effects among CLA+ T cells (IL-22: 11 vs 7.5, P = .04). Severe AD is accompanied by expansion of skin-homing TH2/TC2 and TH22/TC22 subsets with lower TH1/TC1 frequencies. These data create a critical basis for studying alterations in immune activation in adults and pediatric patients with AD. Past studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed before the identification of TH9, TH17, and TH22 T-cell populations in human subjects. We sought to quantify TH1, TH2, TH9, TH17, and TH22 T-cell populations and corresponding CD8(+) T-cell subsets in both cutaneous lymphocyte antigen (CLA)-positive and CLA(-) T-cell subsets in patients with AD and control subjects. We studied 42 adults with severe AD (mean SCORAD score, 65) and 25 healthy subjects using an 11-color flow cytometric antibody panel. Frequencies of IFN-γ-, IL-22-, IL-13-, IL-17-, and IL-9-producing CD4(+) and CD8(+) T cells were compared in CLA(-) and CLA(+) populations. We measured increased TH2/TC2/IL-13(+) and TH22/TC22/IL-22(+) populations (P < .1) in patients with severe AD versus control subjects, with significant differences in CLA(+) T-cell numbers (P < .01). A significantly lower frequency of CLA(+) IFN-γ-producing cells was observed in patients with AD, with no significant differences in CLA(-) T-cell numbers. The CLA(+) TH1/TH2 and TC1/TC2 ratio was highly imbalanced in patients with AD (10 vs 3 [P = .005] and 19 vs 7 [P < .001], respectively). Positive correlations were found between frequencies of IL-13- and IL-22-producing CD4(+) and CD8(+) T cells (r = 0.5 and 0.8, respectively; P < .0001), and frequencies of IL-13-producing CLA(+) cells were also correlated with IgE levels and SCORAD scores. Patients with AD with skin infections had higher CD4(+) IL-22(+) and IL-17(+) cell frequencies, which were highly significant among CLA(-) cells (IL-22: 3.7 vs 1.7 [P < .001] and IL-17: 1.7 vs 0.6 [P < .001]), with less significant effects among CLA(+) T cells (IL-22: 11 vs 7.5, P = .04). Severe AD is accompanied by expansion of skin-homing TH2/TC2 and TH22/TC22 subsets with lower TH1/TC1 frequencies. These data create a critical basis for studying alterations in immune activation in adults and pediatric patients with AD. Past studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed before the identification of TH9, TH17, and TH22 T-cell populations in human subjects.BACKGROUNDPast studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed before the identification of TH9, TH17, and TH22 T-cell populations in human subjects.We sought to quantify TH1, TH2, TH9, TH17, and TH22 T-cell populations and corresponding CD8(+) T-cell subsets in both cutaneous lymphocyte antigen (CLA)-positive and CLA(-) T-cell subsets in patients with AD and control subjects.OBJECTIVEWe sought to quantify TH1, TH2, TH9, TH17, and TH22 T-cell populations and corresponding CD8(+) T-cell subsets in both cutaneous lymphocyte antigen (CLA)-positive and CLA(-) T-cell subsets in patients with AD and control subjects.We studied 42 adults with severe AD (mean SCORAD score, 65) and 25 healthy subjects using an 11-color flow cytometric antibody panel. Frequencies of IFN-γ-, IL-22-, IL-13-, IL-17-, and IL-9-producing CD4(+) and CD8(+) T cells were compared in CLA(-) and CLA(+) populations.METHODSWe studied 42 adults with severe AD (mean SCORAD score, 65) and 25 healthy subjects using an 11-color flow cytometric antibody panel. Frequencies of IFN-γ-, IL-22-, IL-13-, IL-17-, and IL-9-producing CD4(+) and CD8(+) T cells were compared in CLA(-) and CLA(+) populations.We measured increased TH2/TC2/IL-13(+) and TH22/TC22/IL-22(+) populations (P < .1) in patients with severe AD versus control subjects, with significant differences in CLA(+) T-cell numbers (P < .01). A significantly lower frequency of CLA(+) IFN-γ-producing cells was observed in patients with AD, with no significant differences in CLA(-) T-cell numbers. The CLA(+) TH1/TH2 and TC1/TC2 ratio was highly imbalanced in patients with AD (10 vs 3 [P = .005] and 19 vs 7 [P < .001], respectively). Positive correlations were found between frequencies of IL-13- and IL-22-producing CD4(+) and CD8(+) T cells (r = 0.5 and 0.8, respectively; P < .0001), and frequencies of IL-13-producing CLA(+) cells were also correlated with IgE levels and SCORAD scores. Patients with AD with skin infections had higher CD4(+) IL-22(+) and IL-17(+) cell frequencies, which were highly significant among CLA(-) cells (IL-22: 3.7 vs 1.7 [P < .001] and IL-17: 1.7 vs 0.6 [P < .001]), with less significant effects among CLA(+) T cells (IL-22: 11 vs 7.5, P = .04).RESULTSWe measured increased TH2/TC2/IL-13(+) and TH22/TC22/IL-22(+) populations (P < .1) in patients with severe AD versus control subjects, with significant differences in CLA(+) T-cell numbers (P < .01). A significantly lower frequency of CLA(+) IFN-γ-producing cells was observed in patients with AD, with no significant differences in CLA(-) T-cell numbers. The CLA(+) TH1/TH2 and TC1/TC2 ratio was highly imbalanced in patients with AD (10 vs 3 [P = .005] and 19 vs 7 [P < .001], respectively). Positive correlations were found between frequencies of IL-13- and IL-22-producing CD4(+) and CD8(+) T cells (r = 0.5 and 0.8, respectively; P < .0001), and frequencies of IL-13-producing CLA(+) cells were also correlated with IgE levels and SCORAD scores. Patients with AD with skin infections had higher CD4(+) IL-22(+) and IL-17(+) cell frequencies, which were highly significant among CLA(-) cells (IL-22: 3.7 vs 1.7 [P < .001] and IL-17: 1.7 vs 0.6 [P < .001]), with less significant effects among CLA(+) T cells (IL-22: 11 vs 7.5, P = .04).Severe AD is accompanied by expansion of skin-homing TH2/TC2 and TH22/TC22 subsets with lower TH1/TC1 frequencies. These data create a critical basis for studying alterations in immune activation in adults and pediatric patients with AD.CONCLUSIONSSevere AD is accompanied by expansion of skin-homing TH2/TC2 and TH22/TC22 subsets with lower TH1/TC1 frequencies. These data create a critical basis for studying alterations in immune activation in adults and pediatric patients with AD. Background Past studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed before the identification of TH9, TH17, and TH22 T-cell populations in human subjects. Objective We sought to quantify TH1, TH2, TH9, TH17, and TH22 T-cell populations and corresponding CD8+T-cell subsets in both cutaneous lymphocyte antigen (CLA)-positive and CLA-T-cell subsets in patients with AD and control subjects. Methods We studied 42 adults with severe AD (mean SCORAD score, 65) and 25 healthy subjects using an 11-color flow cytometric antibody panel. Frequencies of IFN-γ-, IL-22-, IL-13-, IL-17-, and IL-9-producing CD4+and CD8+T cells were compared in CLA-and CLA+populations. Results We measured increased TH2/TC2/IL-13+and TH22/TC22/IL-22+populations (P < .1) in patients with severe AD versus control subjects, with significant differences in CLA+T-cell numbers (P < .01). A significantly lower frequency of CLA+IFN-γ-producing cells was observed in patients with AD, with no significant differences in CLA-T-cell numbers. The CLA+TH1/TH2 and TC1/TC2 ratio was highly imbalanced in patients with AD (10 vs 3 [P = .005] and 19 vs 7 [P < .001], respectively). Positive correlations were found between frequencies of IL-13- and IL-22-producing CD4+and CD8+T cells (r = 0.5 and 0.8, respectively;P < .0001), and frequencies of IL-13-producing CLA+cells were also correlated with IgE levels and SCORAD scores. Patients with AD with skin infections had higher CD4+IL-22+and IL-17+cell frequencies, which were highly significant among CLA-cells (IL-22: 3.7 vs 1.7 [P < .001] and IL-17: 1.7 vs 0.6 [P < .001]), with less significant effects among CLA+T cells (IL-22: 11 vs 7.5,P = .04). Conclusions Severe AD is accompanied by expansion of skin-homing TH2/TC2 and TH22/TC22 subsets with lower TH1/TC1 frequencies. These data create a critical basis for studying alterations in immune activation in adults and pediatric patients with AD. |
| Author | Czarnowicki, Tali Zheng, Xiuzhong Guttman-Yassky, Emma Gonzalez, Juana Sullivan-Whalen, Mary Suárez-Fariñas, Mayte Khattri, Saakshi Gilleaudeau, Patricia Shemer, Avner Xu, Hui Malajian, Dana Krueger, James G. |
| Author_xml | – sequence: 1 givenname: Tali surname: Czarnowicki fullname: Czarnowicki, Tali email: tczarnowic01@rockefeller.edu organization: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY – sequence: 2 givenname: Juana surname: Gonzalez fullname: Gonzalez, Juana organization: Translational Technology Core Laboratory, Rockefeller University, New York, NY – sequence: 3 givenname: Avner surname: Shemer fullname: Shemer, Avner organization: Department of Dermatology, Tel-Hashomer Hospital, Tel Aviv, Israel – sequence: 4 givenname: Dana surname: Malajian fullname: Malajian, Dana organization: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY – sequence: 5 givenname: Hui surname: Xu fullname: Xu, Hui organization: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY – sequence: 6 givenname: Xiuzhong surname: Zheng fullname: Zheng, Xiuzhong organization: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY – sequence: 7 givenname: Saakshi surname: Khattri fullname: Khattri, Saakshi organization: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY – sequence: 8 givenname: Patricia surname: Gilleaudeau fullname: Gilleaudeau, Patricia organization: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY – sequence: 9 givenname: Mary surname: Sullivan-Whalen fullname: Sullivan-Whalen, Mary organization: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY – sequence: 10 givenname: Mayte surname: Suárez-Fariñas fullname: Suárez-Fariñas, Mayte organization: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY – sequence: 11 givenname: James G. surname: Krueger fullname: Krueger, James G. organization: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY – sequence: 12 givenname: Emma surname: Guttman-Yassky fullname: Guttman-Yassky, Emma organization: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25748064$$D View this record in MEDLINE/PubMed |
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| Keywords | MFI IFN-γ AD Atopic dermatitis cutaneous lymphocyte antigen PMA T cell skin infections ICS CLA IL-13 IL-22 |
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| Snippet | Past studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed before the... Background Past studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed... |
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| SubjectTerms | Adolescent Adult Age Aged Alzheimer's disease Antigens, Differentiation, T-Lymphocyte - metabolism Atopic dermatitis CD8-Positive T-Lymphocytes - immunology Cell Movement Cells, Cultured cutaneous lymphocyte antigen Cytokines Dementia Dermatitis, Atopic - immunology Disease Progression Expansion Female Humans IFN-γ IL-13 IL-22 Immunophenotyping Interleukin-17 - metabolism Interleukin-22 Interleukins - metabolism Lymphocytes Male Membrane Glycoproteins - metabolism Middle Aged Population Skin - immunology skin infections Staphylococcus infections Studies T cell T-Lymphocyte Subsets - immunology Th17 Cells - immunology Th2 Cells - immunology Young Adult |
| Title | Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing T-cell population |
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