Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies

Masutaka Furue; Takahito Chiba; Gaku Tsuji; Dugarmaa Ulzii; Makiko Kido-Nakahara; Takeshi Nakahara; Takafumi Kadono

doi:10.1016/j.alit.2016.12.002

Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies

Allergol Int. 2017 Jul;66(3):398-403. doi: 10.1016/j.alit.2016.12.002. Epub 2017 Jan 2.

Authors

Masutaka Furue¹, Takahito Chiba², Gaku Tsuji³, Dugarmaa Ulzii², Makiko Kido-Nakahara², Takeshi Nakahara⁴, Takafumi Kadono⁵

Affiliations

¹ Department of Dermatology, Kyushu University, Fukuoka, Japan; Research and Clinical Center for Yusho and Dioxin, Kyushu University, Fukuoka, Japan; Division of Skin Surface Sensing, Department of Dermatology, Kyushu University, Fukuoka, Japan. Electronic address: furue@dermatol.med.kyushu-u.ac.jp.
² Department of Dermatology, Kyushu University, Fukuoka, Japan.
³ Department of Dermatology, Kyushu University, Fukuoka, Japan; Research and Clinical Center for Yusho and Dioxin, Kyushu University, Fukuoka, Japan.
⁴ Department of Dermatology, Kyushu University, Fukuoka, Japan; Division of Skin Surface Sensing, Department of Dermatology, Kyushu University, Fukuoka, Japan.
⁵ Department of Dermatology, St. Marianna University School of Medicine, Kanagawa, Japan.

PMID: 28057434
DOI: 10.1016/j.alit.2016.12.002

Abstract

Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder mostly associated with IgE elevation and skin barrier dysfunction due to decreased filaggrin expression. The lesional skin of AD exhibits Th2- and Th22-deviated immune reactions that are progressive during disease chronicity. Th2 and Th22 cytokines further deteriorate the skin barrier by inhibiting filaggrin expression. Some IgEs are reactive to self-antigens. The IgE autoreactivity may precipitate the chronicity of AD. Upon activation of the ORAI1 calcium channel, atopic epidermis releases large amounts of thymic stromal lymphopoietin (TSLP), which initiates the Th2 and Th22 immune response. Th2-derived interleukin-31 and TSLP induce an itch sensation. Taken together, TSLP/Th2/Th22 pathway is a promising target for developing new therapeutics for AD. Enhancing filaggrin expression using ligands for the aryl hydrocarbon receptor may also be an adjunctive measure to restore the disrupted barrier function specifically for AD.

Keywords: Atopic dermatitis; Filaggrin; IgE autoreactivity; Th2; Th22.

Publication types

Review

MeSH terms

Allergens / immunology*
Animals
Autoimmunity*
Combined Modality Therapy
Cytokines / metabolism
Dermatitis, Atopic / immunology*
Dermatitis, Atopic / metabolism
Dermatitis, Atopic / pathology*
Dermatitis, Atopic / therapy
Filaggrin Proteins
Histocompatibility Antigens Class I / immunology
Humans
Immunoglobulin E / immunology*
Inflammation Mediators / metabolism
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism
Th2 Cells / immunology
Th2 Cells / metabolism

Substances

Allergens
Cytokines
FLG protein, human
Filaggrin Proteins
Histocompatibility Antigens Class I
Inflammation Mediators
T22 antigen
Immunoglobulin E