Contrasting pathogenesis of atopic dermatitis and psoriasis—Part II: Immune cell subsets and therapeutic concepts

doi:10.1016/j.jaci.2011.01.054

Journal of Allergy and Clinical Immunology

Volume 127, Issue 6, June 2011, Pages 1420-1432

https://doi.org/10.1016/j.jaci.2011.01.054 Get rights and content

Atopic dermatitis (AD) and psoriasis are among the most common inflammatory skin diseases. In the first part of this 2-part review, we discussed the similarities and differences between AD and psoriasis with respect to clinical features and pathology. The diseases are characterized by infiltration of skin lesions by large numbers of inflammatory cells; the second part of this review focuses on immune cell subsets that distinguish each disease and the therapeutic strategies that might be used or developed based on this information. We discuss the interactions among different populations of immune cells that ultimately create the complex inflammatory phenotype of AD and compare these with psoriasis. Therapeutic strategies have been developed for psoriasis based on the cytokine network that promotes inflammation in this disease. Antibodies against IL-12 and IL-23p40 antibody and antagonists of TNF are used to treat patients with psoriasis, and studies are underway to test specific antagonists of IL-23, IL-17, IL-17 receptor, IL-20, and IL-22. We discuss how these therapeutic approaches might be applied to AD.

Section snippets

T cells

Recruitment of T cells into the skin and their effector responses are considered to be key features in the pathogenesis of AD and psoriasis.4, 8, 9, 10 In both diseases T cells that bear a specialized skin-homing receptor, the cutaneous lymphocyte antigen (CLA), are present in skin lesions. This antigen is defined by the mAb HECA-452.¹¹ Most CLA⁺ T cells reside in normal skin, with only a small fraction in the peripheral circulation; AD and psoriasis involve expansion of CLA⁺ cell subsets.12, 13

Mast cells and eosinophils

Mast cells and eosinophils often colocalize during the development of allergic or parasitic diseases. In patients with allergic diseases, mast cells might amplify IgE-mediated inflammation and eosinophil influx to tissues (Fig 1, Fig 2).⁶⁸

Mast cells have important roles in inflammation: they regulate eosinophil activation and recruitment. These potent granulated cells are often the first to respond to challenge with an antigen and initiate an immune response.69, 70 They have FcεRI on their

Keratinocytes and the inflammatory response

In skin from patients with AD or psoriasis, alterations in keratinocyte function not only cause the most visible alterations and symptoms, but keratinocytes also produce inflammatory factors that promote chronic, self-amplifying loops of immune activation.9, 24, 43, 90 The epidermis functions as not only a physical barrier but also a chemical and immunologic barrier; it produces many inflammatory mediators, including cytokines, chemokines, S100 proteins, and AMPs.

Two examples illustrate the

Innate and adaptive immunity and defects in the epidermal barrier

Defects in immune and epidermal barrier function might have overlapping effects that contribute to AD and psoriasis.15, 17 During the development of AD, the T_H2 cell cytokines IL-4 and IL-13 modify keratinocyte responses (Fig 2, A) and inhibit production of terminal differentiation proteins, including loricrin, filaggrin, and involucrin,15, 17, 18 and/or AMPs.16, 17 Additionally, T22 cell production of IL-22 is upregulated in skin lesions of patients with AD compared with that seen in healthy

Therapeutics

Psoriasis is a useful model for studying targeted therapies for inflammatory diseases because areas of diseased skin can clearly be distinguished from normal skin using quantitative and qualitative biomarkers of epidermal hyperplasia. Furthermore, active psoriasis can be completely reversed, such that biopsy samples from treated lesions cannot be distinguished from those from normal skin. Treatment time is also short. Symptoms of the disease can usually be completely reversed within 8 to 12

Conclusion

Psoriasis develops through well-understood mechanisms and has many treatment options, including targeted biologics with proved efficacy, whereas our understanding of AD’s pathogenesis and treatment is limited. AD and psoriasis are characterized by equally complex immunologic interactions, but broad-spectrum agents that inhibit production of T_H2 cytokines and chemokines might be the best therapeutic approach for AD. Strategies that include a combination of more than 1 biologic agent or a

Immune mechanisms

1.
Is AD initiated by an increased response by T_H2 cells or reduced response by T_H1 cells? What are the roles of T cells and DCs in determining whether the response is mediated by T_H1 or T_H2 cells?
2.
Patients with AD to not have adequate T_H1 cell responses. Is this because of exposures to specific antigens or bacteria or lack of exposure?
3.
What is the role of T_H17 and T22 cells in disease induction? Do T22 cells have an active role in induction of disease (acute stage), or do they function only in

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Clinical overlaps between psoriasis and atopic dermatitis (AD) are sometimes undiscernible, and there is no consensus on whether to treat the overlap phenotype as psoriasis or AD. We enrolled 41 patients diagnosed with either psoriasis or AD and clinically re-stratified them into classic psoriasis (n = 11), classic AD (n = 13), and the overlap phenotype between psoriasis and AD (n = 17). We compared the gene expression profiles of lesional and nonlesional skin biopsy tissues and the proteomic profiles of blood samples among the three comparison groups. Global mRNA expression and T-cell subset cytokine expression in the skin and protein biomarker elevation in the blood of the overlap phenotype were consistent with the profiles of psoriasis and different from the profiles of AD. Unsupervised k-means clustering indicated that the best number of distinct clusters for the total population of the three comparison groups was two, and the two clusters of psoriasis and AD were differentiated by gene expression. Our study suggests that the clinical overlap phenotype between psoriasis and AD has dominant molecular features of psoriasis, and genomic biomarkers can differentiate psoriasis and AD at molecular levels in patients with a spectrum of psoriasis and AD.
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Immunologically targeted therapies have revolutionized the treatment of inflammatory dermatoses, including atopic dermatitis and psoriasis. Although immunologic biomarkers hold great promise for personalized classification of skin disease and tailored therapy selection, there are no approved or widely used approaches for this in dermatology. This review summarizes the translational immunologic approaches to measuring treatment-relevant biomarkers in inflammatory skin conditions. Tape strip profiling, microneedle-based biomarker patches, molecular profiling from epidermal curettage, RNA in situ hybridization tissue staining, and single-cell RNA sequencing have been described. We discuss the advantages and limitations of each and open questions for the future of personalized medicine in inflammatory skin disease.
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: Disclosure of potential conflict of interest: E. Guttman-Yassky and K. E. Nograles have declared that they have no conflict of interest. J. G. Krueger has consulted for Amgen, Anacor Pharmaceuticals, Centocor, Gateway Pharmaceuticals, Idera Pharmaceuticals, and Pfizer; has performed investigations for Boehringer Ingelheim, Eli Lilly, and Merck; has served on an advisory board for Janssen; and has received research support (through Rockefeller University) from Amgen, Centocor, Merck, and Eli Lilly.

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Reviews and feature articleContrasting pathogenesis of atopic dermatitis and psoriasis—Part II: Immune cell subsets and therapeutic concepts

Section snippets

T cells

Mast cells and eosinophils

Keratinocytes and the inflammatory response

Innate and adaptive immunity and defects in the epidermal barrier

Therapeutics

Conclusion

Immune mechanisms

J Allergy Clin Immunol

J Allergy Clin Immunol

J Invest Dermatol

J Allergy Clin Immunol

J Allergy Clin Immunol

Clin Immunol

J Invest Dermatol

J Allergy Clin Immunol

J Invest Dermatol

J Invest Dermatol

J Allergy Clin Immunol

Clin Immunol

J Allergy Clin Immunol

Immunol Allergy Clin North Am

Trends Immunol

Clin Dermatol

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Immunity

J Allergy Clin Immunol

J Invest Dermatol

Immunobiology

Lancet

J Allergy Clin Immunol

Curr Opin Immunol

Adv Immunol

Genomics

J Allergy Clin Immunol

J Allergy Clin Immunol

J Invest Dermatol

Immunity

Facing psoriasis and atopic dermatitis: are there more similarities or more differences?

Eur J Dermatol

Atopic dermatitis

Ann Dermatol

Cytokine-producing dendritic cells in the pathogenesis of inflammatory skin diseases

J Clin Immunol

Pathogenesis and therapy of psoriasis

Nature

Psoriasis

N Engl J Med

Functional evidence that the HECA-452 antigen is involved in the adhesion of human neutrophils and lymphocytes to tumour necrosis factor-alpha-stimulated endothelial cells

Immunology

CCL18 is expressed in atopic dermatitis and mediates skin homing of human memory T cells

J Immunol

Circulating CLA+ T cell subsets inversely correlate with disease severity and extension in acute psoriasis but not in chronic plaque psoriasis

Eur J Dermatol

Low expression of the IL-23/Th17 pathway in atopic dermatitis compared to psoriasis

J Immunol

Recent insights into atopic dermatitis and implications for management of infectious complications

J Allergy Clin Immunol

Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis

J Allergy Clin Immunol

IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells

J Allergy Clin Immunol

Interleukin-17 in inflammatory skin disorders

Curr Opin Allergy Clin Immunol

IL-17 and Th17 Cells

Annu Rev Immunol

Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways

Br J Dermatol

New insights in the immunologic basis of psoriasis

Semin Cutan Med Surg

Reviews and feature article
Contrasting pathogenesis of atopic dermatitis and psoriasis—Part II: Immune cell subsets and therapeutic concepts