1. The <scp>IL</scp> ‐13– <scp>OVOL</scp> 1– <scp>FLG</scp> axis in atopic dermatitis
- Author
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Takeshi Nakahara, Kazuhisa Furue, Dugarmaa Ulzii, Masutaka Furue, Gaku Tsuji, Yen Hai Vu, Takamichi Ito, and Makiko Kido-Nakahara
- Subjects
0301 basic medicine ,Immunology ,Inflammation ,Filaggrin Proteins ,Antibodies, Monoclonal, Humanized ,Dermatitis, Atopic ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Intermediate Filament Proteins ,medicine ,Animals ,Humans ,Immunology and Allergy ,Lymphocytes ,Review Articles ,Skin ,Interleukin-13 ,business.industry ,Innate lymphoid cell ,Antibodies, Monoclonal ,Interleukin-4 Receptor alpha Subunit ,Atopic dermatitis ,medicine.disease ,Dupilumab ,Immunity, Innate ,Biological Therapy ,DNA-Binding Proteins ,030104 developmental biology ,Interleukin 13 ,medicine.symptom ,business ,Signal Transduction ,Transcription Factors ,030215 immunology ,Tralokinumab ,Filaggrin - Abstract
Despite sharing interleukin‐4 receptor α (IL‐4Rα) in their signaling cascades, IL‐4 and IL‐13 have different functions in atopic inflammation. IL‐13 preferentially participates in the peripheral tissues because tissue‐resident group 2 innate lymphoid cells produce IL‐13 but not IL‐4. In contrast, lymph node T follicular helper cells express IL‐4 but not IL‐13 to regulate B‐cell immunity. The dominant microenvironment of IL‐13 is evident in the lesional skin of atopic dermatitis (AD). The IL‐13‐rich local milieu causes barrier dysfunction by down‐regulating the OVOL1–filaggrin (FLG) axis and up‐regulating the periostin–IL‐24 axis. Genome‐wide association studies also point to the crucial involvement of the IL‐13, OVOL1 and FLG genes in the pathogenesis of AD. Biologics targeting IL‐13, such as the anti‐IL‐4Rα antibody dupilumab and the anti‐IL‐13 antibody tralokinumab, successfully improve AD lesions and further highlight the importance of IL‐13 in the pathogenesis of AD.
- Published
- 2019