Distinct expression of interleukin (IL)-36α, β and γ, their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn's disease
Distinct expression of interleukin (IL)-36α, β and γ, their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn's disease
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DOI：
10.1111/cei.12761
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发表时间：
2016-05-01
影响因子：
4.6
通讯作者：
Blanchard, F.
中科院分区：
文献类型：
--
作者：
Boutet, M. -A.;Bart, G.;Blanchard, F.
白细胞介素（IL）-36α、IL - 36β和IL - 36γ在皮肤中高表达，并参与银屑病的发病机制，而拮抗剂IL - 36Ra或IL - 38（另一种潜在的IL - 36抑制剂）可限制不受控制的炎症。IL - 36细胞因子在类风湿关节炎（RA）和克罗恩病（CD）中的表达及作用目前存在争议。在此，我们观察到在咪喹莫特诱导的小鼠皮肤炎症以及人类银屑病中，IL - 36α和IL - 36Ra的表达被诱导，且与IL - 1和辅助性T细胞17型（Th17）细胞因子（IL - 17A、IL - 22、IL - 23、CCL20）相关，但IL - 36γ和IL - 38的mRNA未被诱导。在胶原诱导性关节炎小鼠以及类风湿关节炎患者的滑膜中，IL - 36α、IL - 36β、IL - 36γ、IL - 36Ra和IL - 38均升高，并与IL - 1、CCL3、CCL4和巨噬细胞集落刺激因子（M - CSF）相关，但与Th17细胞因子无关。在葡聚糖硫酸钠诱导的结肠炎小鼠的结肠以及克罗恩病患者中，只有IL - 36α和IL - 38在相对较低水平被诱导，并与IL - 1和IL - 17A相关。我们认为，只有少数类风湿关节炎患者（17% - 29%）或克罗恩病患者（25%）的IL - 36激动剂/拮抗剂比值升高，而银屑病患者中这一比例为93%。通过免疫组织化学方法，IL - 36细胞因子由皮肤、滑膜和结肠黏膜中的多种细胞类型产生，如角质形成细胞、CD68⁺巨噬细胞、树突状/朗格汉斯细胞和CD79⁺浆细胞。在单核细胞或炎性巨噬细胞（M1）的原代培养中，IL - 36α和IL - 36Ra组成性产生，但IL - 36γ和IL - 38在脂多糖刺激后产生。这些不同的表达谱可能有助于解释为什么只有部分类风湿关节炎和克罗恩病患者具有潜在升高的IL - 36激动剂/拮抗剂比值。
Interleukin (IL)-36, IL-36 and IL-36 are expressed highly in skin and are involved in the pathogenesis of psoriasis, while the antagonists IL-36Ra or IL-38, another potential IL-36 inhibitor, limit uncontrolled inflammation. The expression and role of IL-36 cytokines in rheumatoid arthritis (RA) and Crohn's disease (CD) is currently debated. Here, we observed that during imiquimod-induced mouse skin inflammation and in human psoriasis, expression of IL-36, and IL-36Ra, but not IL-36 and IL-38 mRNA, was induced and correlated with IL-1 and T helper type 17 (Th17) cytokines (IL-17A, IL-22, IL-23, CCL20). In mice with collagen-induced arthritis and in the synovium of patients with RA, IL-36, , , IL-36Ra and IL-38 were all elevated and correlated with IL-1, CCL3, CCL4 and macrophage colony-stimulating factor (M-CSF), but not with Th17 cytokines. In the colon of mice with dextran sulphate sodium-induced colitis and in patients with CD, only IL-36, and IL-38 were induced at relatively low levels and correlated with IL-1 and IL-17A. We suggest that only a minor subgroup of patients with RA (17-29%) or CD (25%) had an elevated IL-36 agonists/antagonists ratio, versus 93% of patients with psoriasis. By immunohistochemistry, IL-36 cytokines were produced by various cell types in skin, synovium and colonic mucosa such as keratinocytes, CD68(+) macrophages, dendritic/Langerhans cells and CD79(+) plasma cells. In primary cultures of monocytes or inflammatory macrophages (M1), IL-36 and IL-36Ra were produced constitutively, but IL-36, and IL-38 were produced after lipopolysaccharide stimulation. These distinct expression profiles may help to explain why only subgroups of RA and CD patients have a potentially elevated IL-36 agonists/antagonists ratio.