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.
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.
Laboratory for Investigative Dermatology, Rockefeller University, New York, NY. Electronic address: tczarnowic01@rockefeller.edu.
Tali
T
Czarnowicki
Translational Technology Core Laboratory, Rockefeller University, New York, NY.
Juana
J
Gonzalez
Department of Dermatology, Tel-Hashomer Hospital, Tel Aviv, Israel.
Avner
A
Shemer
Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Columbia University College of Physicians and Surgeons, New York, NY.
Dana
D
Malajian
Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
Hui
H
Xu
Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
Xiuzhong
X
Zheng
Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
Saakshi
S
Khattri
Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
Patricia
P
Gilleaudeau
Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
Mary
M
Sullivan-Whalen
Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Center for Clinical and Translational Science, Rockefeller University, New York, NY.
Mayte
M
Suárez-Fariñas
Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
James G
JG
Krueger
Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Dermatology Department at the Icahn School of Medicine at Mount Sinai, New York, NY.
Emma
E
Guttman-Yassky
D000293:Adolescent; D000328:Adult; D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D012867:Skin / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D055815:Young Adult; D000097043:Interleukin-22
D000945:Antigens, Differentiation, T-Lymphocyte; D020381:Interleukin-17; D007378:Interleukins; D008562:Membrane Glycoproteins; D000097043:Interleukin-22; C063419:CTAGE1 protein, human
Atopic dermatitis; IFN-γ; IL-13; IL-22; T cell; cutaneous lymphocyte antigen; skin infections