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Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction and chronic pruritus. Excellent clinical efficacy of the anti-interleukin-4 (IL-4) receptor α antibody dupilumab underpins the pivotal roles of T helper type 2 (Th2) cytokines IL-13 and IL-4 in the pathogenesis of AD. Th2 cells also produce IL-31 which is the most important pruritogenic cytokine in AD. IL-13 and IL-4 downregulate the expression of filaggrin in keratinocytes and exacerbate epidermal barrier dysfunction. Keratinocytes in barrier-disrupted epidermis produce large amounts of thymic stromal lymphopoietin, IL-25 and IL-33, which contribute to Th2 immune deviation via OX40L/OX40 signaling. IL-13 and IL-4 also amplify the IL-31-mediated pruritus. In this review, I summarize recent advances in the pathogenesis of AD.

Excessive sputum due to airway hypersecretion is one of the common symptoms in respiratory diseases such as asthma and bronchiectasis. Airway secretion is mainly composed of mucin from airway goblet cells and submucosal glands and water through ion transport in airway epithelial cells. Although airway secretion plays an important role in defense mechanism, the increase in intraluminal mucus may lead to the impairment of mucociliary clearance and airway obstruction. Airway secretion is stimulated by autonomic nervous system and a variety of chemical mediators, but these mechanisms are different under individual conditions. It is thus important to select mucoregulating drugs after understanding the pathophysiology of hypersecretion. Recent evidence suggests that goblet cell hyperplasia and mucin overproduction are associated with Th2 cytokines such as IL-13, EGF-receptor, and Ca activated Cl channels. The new therapeutic approach based on the evidence could be developed in the future.

Th2型サイトカインの1つであるインターロイキン（IL）-13はアトピー性皮膚炎、強皮症、乾癬、喘息、炎症性腸疾患、ホジキンリンパ腫など多くの疾患で発現亢進が報告されている。IL-13は線維芽細胞の増殖、コラーゲン生成を促進し、接着因子や線維芽細胞からのprofibrotic cytokine発現を増強する作用をもち、コラーゲンゲルの収縮にも関与すると考えられている。一方、アトピー性皮膚炎の病変部真皮の単核球や表皮樹状細胞ではIL-13発現が認められ、慢性病変では表皮肥厚とともにI型コラーゲンの増加による真皮の線維化が認められる。真皮の線維化はコラーゲンを含む細胞外マトリックス(ECM)の増加に他ならない。これまでもIL-13はECM産生やMMP産生に関わり、組織の線維化に関連があると報告されているが不明な部分も多い。本研究では、IL-13による真皮線維化の機序を明らかにすることで、アトピー性皮膚炎の病態に対する理解を深めることを目的とした。