Elevated IL-22 in psoriasis plays an anti-apoptotic role in keratinocytes through mediating Bcl-xL/Bax
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Elevated IL‑22 in psoriasis plays an anti‑apoptotic role in keratinocytes through mediating Bcl‑xL/Bax Bo Wang2 · Dan Han1 · Fei Li1 · Weikun Hou3,4 · Lijuan Wang1 · Liesu Meng3 · Kuanhou Mou1 · Shemin Lu3 · Wenhua Zhu3 · Yan Zhou1
© The Author(s) 2020
Abstract IL-22 is known to mediate inflammation in psoriasis, while IL-22 binding protein (IL-22BP) binds IL-22 to suppress IL-22 signaling. However, the function of IL-22 in regulating apoptosis in psoriasis remains poorly understood. In this study, we found that IL-22/IL-22R1 in lesional skin and IL-22 in serum from psoriatic patients were highly upregulated compared with healthy controls, while IL-22BP was not changed. Correlations between IL-22/IL-22R1 levels and the thickness of psoriatic lesions suggested that IL-22 might positively regulate abnormal hyperplasia in psoriasis. Apoptotic keratinocytes were increased only in stratum corneum, but not in spinous and basal layers of psoriasis. Moreover, IL-22 promoted cell viability in human epidermal keratinocytes (HEKs). The apoptosis induced by TNF-α and IFN-γ was inhibited in HEKs treated with IL-22, since that IL-22 upregulated Bcl-xL and downregulated Bax production in HEKs in the presence of TNF-α and IFN-γ. In addition, IL-22BP could counteract the anti-apoptotic effect of IL-22. Our finding demonstrates that IL-22 might play an anti-apoptosis role on keratinocytes to balance cell proliferation and apoptosis in psoriatic epidermis. Keywords IL-22 · Psoriasis · Anti-apoptosis · Keratinocytes · Bcl-xL/Bax
Introduction Psoriasis is widely regarded as a chronic autoimmune disease with an incidence of approximately 1% to 10% in the world [1, 2], characterized by protuberant clinical features of scaly patches on the skin. Prominent pathological features Bo Wang, Dan Han, Wenhua Zhu and Yan Zhou contributed equally to this work * Wenhua Zhu [email protected] * Yan Zhou [email protected]; [email protected] 1
Department of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
2
Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
3
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, China
4
Osteonecrosis and Joint Reconstruction Ward, Joint Surgery, Xi’an Honghui Hospital, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, China
are keratinocyte hyperproliferation, incompletely differentiated epidermal keratinocytes, and abnormal keratinocyte apoptosis, which might be one of the key pathogenetic mechanisms in psoriasis [3]. In recent years, Th22 cells were proposed as a new helper T cell subset, and subsequent studies found that Th22 cells were involved in the pathogenesis of various autoimmune diseases, including psoriasis [4]. IL-22 is the representative cytokine of Th22 cells, whose membrane-bound IL-22 receptor 1 (IL-22R1) is crucial for maintaining cutaneous
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