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 - 03/07/15
, Juana Gonzalez, PhD b, ∗, Avner Shemer, MD c, ∗, Dana Malajian, BA a, e, Hui Xu, MSc a, Xiuzhong Zheng, MSc a, Saakshi Khattri, MD a, Patricia Gilleaudeau, NP a, Mary Sullivan-Whalen, NP a, Mayte Suárez-Fariñas, PhD a, d, James G. Krueger, MD, PhD a, Emma Guttman-Yassky, MD, PhD a, fAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Atopic dermatitis, T cell, cutaneous lymphocyte antigen, IL-13, IL-22, IFN-γ, skin infections
Abbreviations used : AD, CLA, ICS, MFI, PMA
Plan
| T.C. was supported in part by grant no. UL1 TR000043 from the National Center for Advancing Translational Science Award (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program. J.G. was supported in part by grant no. UL1TR0000 from the NCATS, NIH CTSA program. D.M. received funding from the American Dermatological Association Medical Student Fellowship. J.G.K. and M.S.-F. were supported by grant no. 5UL1RR024143-02 from the National Center for Research Resources (NCRR), a component of the NIH, and the NIH Roadmap for Medical Research. E.G.-Y. was supported by the Dermatology Foundation Physician Scientist Career Development Award. |
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| Disclosure of potential conflict of interest: J. G. Krueger has received personal fees and money to his institution from Pfizer, Janssen, Lilly, Merck, Novartis, Kadmon, Dermira, Boehringer, and BMS; has received money to his institution only from Amgen, Innovaderm, Kyowa, and Parexel; and has received personal fees only from Serono, Biogen Idec, Delenex, AbbVie, Sanofi, Baxter, Xenoport, and Kineta. E. Guttman-Yassky has board memberships with Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, Medimmune, Celgene, Anacor, and Leo Pharma; has consultant arrangements with Regeneron, Sanofi Aventis, Medimmune, Celgene, Steifel/GlaxoSmithKline, Celsus, BMS, Amgen, and Drais; and has received research support from Regeneron, Celgene, BMS, and Janssen. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 136 - N° 1
P. 104 - juillet 2015 Retour au numéro
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