Pathological Mechanisms of Skin Homing T Cells in Atopic Dermatitis

Ferrán, Marta; Santamaria‐Babí, Luis F.

doi:10.1097/wox.0b013e3181d675f8

Cited by 26 publications

(33 citation statements)

References 39 publications

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“…8, 9–11 Most T-cells in AD lesions are CD45RO + memory cells that express the skin-homing receptor cutaneous lymphocyte antigen (CLA). 12–14 Circulating CLA + T-cells are expanded in AD, respond to skin-associated allergens, and play a role in disease pathogenesis. 14–17 CLA + T-cells have been also demonstrated to be peripheral biomarkers in several inflammatory skin diseases.…”

Section: Introductionmentioning

confidence: 99%

Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire CLA+ TH22/TC22 cell subsets

Czarnowicki

Esaki

Gonzalez

et al. 2015

Journal of Allergy and Clinical Immunology

190

171

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Background Identifying differences and similarities between CLA+ polarized T-cell subsets in pediatric vs. adult atopic dermatitis (AD) is critical for directing new treatments towards children. Objective To compare activation markers and frequencies of skin-homing (CLA+) vs. systemic (CLA−) “polar” CD4 and CD8 T-cell subsets in early pediatric AD, adult AD and controls. Methods Flow cytometry was used to measure CD69/ICOS/HLA-DR frequency in memory subsets as well as IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines, defining Th1/Tc1, Th2/Tc2, Th9/Tc9, Th17/Tc17, and Th22/Tc22 populations in CD4 and CD8 cells, respectively. We compared peripheral blood from 19 children <5 years and 42 adults with well-characterized moderate to severe AD, as well as age-matched controls (17 children and 25 adults). Results Selective ICOS activation (P<0.001) was seen in children. CLA+ Th2 T-cells were markedly expanded in both AD children and adults compared to controls, but decreases in CLA+ Th1 T-cells were greater in AD children (17% vs. 7.4%, P=0.007). Unlike in adults, no imbalances were detected in pediatric AD CLA− T-cells, nor were there altered frequencies of Th22 T-cells within CLA+ or CLA− compartments. Adults with AD had increased frequency of IL-22-producing CD4 and CD8 T-cells within the skin-homing population (9.5% vs. 4.5%; 8.6% vs. 2.4%, respectively; P<0.001) as well as increased HLA-DR activation (P<0.01). Conclusions These data suggest that Th2 activation within skin-homing T-cells may drive AD in children and that reduced counter-regulation by Th1 T-cells may contribute to excess Th2 activation. Th22 “spreading” of AD is not seen in young children and may be influenced by immune development, disease chronicity or recurrent skin infections. Clinical Implications Therapeutic approaches to treat AD in children may be best directed to correction of Th2/Th1 imbalance, while adults might also benefit from IL-22 targeted therapies.

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Section: Introductionmentioning

confidence: 99%

Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire CLA+ TH22/TC22 cell subsets

Czarnowicki

Esaki

Gonzalez

et al. 2015

Journal of Allergy and Clinical Immunology

190

171

View full text Add to dashboard Cite

show abstract

“…CLA 1 T cells are specialized for skin homing and represent the main population in AD lesions. [16][17][18][19] Few studies have examined polar T-cell subsets in CLA 1 versus CLA 2 T cells of patients with AD and control subjects. [20][21][22][23] Although some T H 2 expansion is seen in healthy subjects in CLA 1 T cells, additional expansion of this T-cell subset is seen in patients with AD.…”

mentioning

confidence: 99%

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

Czarnowicki

Gonzalez

Shemer³

et al. 2015

Journal of Allergy and Clinical Immunology

189

182

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“…Nickel is a transition element with high biological activity and it is involved in the pathology of allergic diseases including atopic dermatitis [5,6]. Atopic dermatitis is the most frequent chronic skin disease that is regulated by genetic and environmental factors including contaminators like nickel that influence to biology of the immune cells migrating between blood circulation and skin [5][6][7]. The defect of skin barrier and the immune system dysfunction play a major role in the skin hyperactivity of atopic dermatitis [8].…”

Section: Introductionmentioning

confidence: 99%