Progressive activation of Th2/Th22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis
By J. Gittler, A. Shemer, M. Suárez‐Fariñas, J. Fuentes-Duculan, Kara J Gulewicz, Claire Q. F. Wang, H. Mitsui, I. Cardinale, C. de Guzman Strong, J. Krueger and 1 more. Journal of Allergy and Clinical Immunology, 2012
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Background Atopic dermatitis (AD) is a common disease, with an increasing prevalence. The primary pathogenesis of the disease is still elusive, resulting in the lack of specific treatments. AD is currently considered a biphasic disease, with Th2 predominating acute disease, and a switch to Th1 characterizing chronic disease. Elucidation of the molecular factors that participate in the onset of new lesions and maintenance of chronic disease is critical for the development of targeted therapeutics. Objectives We sought to characterize the mechanisms underlying onset and maintenance of AD. Methods We investigated intrapersonal sets of transcriptomes from non-lesional, acute and chronic lesions of ten AD patients through genomic, molecular and cellular profiling. Results Our study associated the onset of acute lesions with a striking increase in a subset of terminal differentiation proteins, specifically the cytokine-modulated S100A7, S100A8, and S100A9. Acute disease was also associated with significant increases in gene expression levels of major Th22- and Th2- cytokines, and smaller increases in IL-17. A lesser induction of Th1-associated genes was detected in acute disease, although some were significantly up-regulated in chronic disease. Further significant intensification of major Th22 and Th2 cytokines was observed between acute and chronic lesions. Conclusions Our data identified increased S100A7, S100A8 and S100A9 gene expression with AD initiation, and concomitant activation of Th2 and Th22 cytokines. Our findings support a model of progressive activation of Th2 and Th22 immune axes from acute to chronic phases, expanding the prevailing view of pathogenesis, with important therapeutic implications.
Subfields: Dermatology, Immunology, Physiology
View Paper: https://www.semanticscholar.org/paper/744ce5e8adb90d85718853c424d1baa366d889ca
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Citations in the corpus
- Epidemiology of atopic dermatitis in adults: Results from an international survey (2018, background): “The clinical presentation of AD includes pruritus, xerosis, and eczematous lesions, and its pathology is characterized by interactions between skin barrier defects and immune dysregulation, with recent evidence suggesting that it is a systemic disorder.(1,2) There is a consistent association of AD w”
- Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch (2017, positive): “Sensory Neurons Are Directly Activated by Type 2 Cytokines Although type 2 cytokines are well-established mediators of skin inflammation in AD (Gittler et al., 2012; Weidinger and Novak, 2016), it is not clear how these cytokines promote chronic itch.”
- The Atopic March: Progression from Atopic Dermatitis to Allergic Rhinitis and Asthma (2014, background): “Studies have also demonstrated exaggerated expression of IL-13 and IL-22 in both acute and chronic lesions of patients with AD [74].”