Reviews and feature articleContrasting pathogenesis of atopic dermatitis and psoriasis—Part II: Immune cell subsets and therapeutic concepts
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 TH2 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 TH2 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 TH2 cells or reduced response by TH1 cells? What are the roles of T cells and DCs in determining whether the response is mediated by TH1 or TH2 cells?
- 2.
Patients with AD to not have adequate TH1 cell responses. Is this because of exposures to specific antigens or bacteria or lack of exposure?
- 3.
What is the role of TH17 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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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.