Furue Kazuhisa, Yamamura Kazuhiko, Tsuji Gaku, Mitoma Chikage, Uchi Hiroshi, Nakahara Takeshi, Kido-Nakahara Makiko, Kadono Takafumi, Furue Masutaka
Department of Dermatology, Kyushu University, Maidashi 3-1-1, Higashiku, Fukuoka, 812-8582, Japan.
Acta Derm Venereol. 2018 Jan 12;98(1):5-13. doi: 10.2340/00015555-2808.
Plaque psoriasis and pustular psoriasis are overlapping, but distinct, disorders. The therapeutic response to biologics supports the pivotal role of the tumour necrosis alpha (TNF-?)/ interleukin (IL)-23/IL-17/IL-22 axis in the pathogenesis of these disorders. Recently, functional activation of the IL-36 receptor (IL-36R) was discovered to be another driving force in the pathogenesis of psoriasis. This was first highlighted by the discovery that a loss-of-function mutation of the IL-36R antagonist (IL-36Ra) causes pustular psoriasis. Although the TNF-?/IL-23/IL-17/IL-22 axis and the functional activation of IL-36R are fundamentally involved in plaque psoriasis and pustular psoriasis, respectively, the 2 pathways are closely related and mutually reinforced, resulting in full-blown clinical manifestations. This review summarizes current topics on how IL-36 agonists (IL-36?, IL-36?, IL-36?) signal IL-36R, the pathological expression of IL-36 agonists and IL-36Ra in plaque and pustular psoriatic lesions, and the cross-talk between the TNF-?/IL-23/IL-17/IL-22 axis and the functional activation of IL-36R in the epidermal milieu.
斑块状银屑病和脓疱型银屑病是相互重叠但又截然不同的疾病。对生物制剂的治疗反应支持肿瘤坏死因子α（TNF-α）/白细胞介素（IL）-23/IL-17/IL-22轴在这些疾病发病机制中的关键作用。最近，白细胞介素36受体（IL-36R）的功能激活被发现是银屑病发病机制中的另一个驱动力。这首先通过发现IL-36R拮抗剂（IL-36Ra）的功能丧失突变会导致脓疱型银屑病而得到凸显。尽管TNF-α/IL-23/IL-17/IL-22轴和IL-36R的功能激活分别在斑块状银屑病和脓疱型银屑病中起根本作用，但这两条途径密切相关且相互强化，导致出现全面的临床表现。这篇综述总结了关于IL-36激动剂（IL-36α、IL-36β、IL-36γ）如何向IL-36R发出信号、IL-36激动剂和IL-36Ra在斑块状和脓疱型银屑病皮损中的病理表达，以及TNF-α/IL-23/IL-17/IL-22轴与表皮环境中IL-36R功能激活之间相互作用的当前研究课题。
