Interleukin-22 secreted by ectopic endometrial stromal cells and natural killer cells promotes the recruitment of macrophages through promoting CCL2 secretion
Interleukin-22 secreted by ectopic endometrial stromal cells and natural killer cells promotes the recruitment of macrophages through promoting CCL2 secretion
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异位子宫内膜基质细胞和自然杀伤细胞分泌的白介素22通过促进CCL2分泌促进巨噬细胞的募集
DOI：
10.1111/aji.13166
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发表时间：
2019
影响因子：
3.6
通讯作者：
Sun Hai Xiang
中科院分区：
文献类型：
--
作者：
Mei Jie;Zhou Wen Jie;Li Shi Yuan;Li Ming Qing;Sun Hai Xiang
问题：在子宫内膜异位症中，功能失调的巨噬细胞数量增加;然而，巨噬细胞募集的机制尚不清楚。本研究的目的是确定自然杀伤（NK）细胞介导的子宫内膜间质细胞（ESCs）分泌趋化因子（C-C motif）配体2（CCL 2）在巨噬细胞募集中的作用。研究方法将正常ESCs（nESC）和异位ESCs（eESC）分别与NK细胞共培养，进行巨噬细胞趋化试验，并计数趋化性巨噬细胞的数量。ELISA法检测细胞内白细胞介素-22（IL-22）的表达，流式细胞仪检测细胞内IL-22受体的表达。用0.01、0.1和1 ng/mL重组人IL-22（rhIL-22）处理eESC，以确定刺激CCL 2产生的最有效浓度。用1 ng/mL rhIL-22处理后，eESC单培养和eESC/NK共培养均检测到CCL 2的分泌。结果与eESC单培养相比，eESC/NK共培养招募了大量趋化性巨噬细胞。与单一培养相比，当eESC共培养时，IL-22和CCL 2分泌的水平也增加。rhIL-22处理导致eESC分泌的CCL 2水平增加，IL-22拮抗剂αIL-22逆转了IL-22诱导的CCL 2分泌。结论NK细胞刺激eESCs分泌IL-22和CCL 2参与巨噬细胞募集，并参与子宫内膜异位症的发生发展。
ProblemDuring endometriosis, there is an increase in the number of dysfunctional macrophages; however, the mechanisms underlying macrophage recruitment are not well understood. The aim of the present study was to determine the role of natural killer (NK) cell‐mediated secretion of chemokine (C‐C motif) ligand 2 (CCL2) from endometrial stromal cells (ESCs) in the recruitment of macrophages.Method of studyNormal ESCs (nESC) and ectopic ESCs (eESCs) were separately co‐cultured with NK cells for a macrophage chemotaxis assay, and the number of chemotactic macrophages was counted. The expression of interleukin‐22 (IL‐22) and IL‐22 receptors was detected by ELISA and flow cytometry, respectively. eESCs were treated with 0.01, 0.1, and 1 ng/mL recombinant human IL‐22 (rhIL‐22) to determine the most effective concentration for stimulating CCL2 production. Following treatment with 1 ng/mL rhIL‐22, secretion of CCL2 was detected from both the eESC monoculture and the eESC/NK co‐culture.ResultsCompared with the eESC monoculture, the eESC/NK co‐culture recruited a significantly higher number of chemotactic macrophages. There was also an increase in the levels of IL‐22 and CCL2 secreted when eESCs were co‐cultured compared with the monoculture. Treatment with rhIL‐22 resulted in an increase in the levels of CCL2 secreted by eESCs, and the IL‐22‐induced CCL2 secretion was reversed by the IL‐22 antagonist, αIL‐22. Increased expression of IL‐22 resulted in an increase in the number of chemotactic macrophages, but was reversed by αIL‐22 and CCL2 antagonist (αCCL2).ConclusionInterleukin‐22 and CCL2 secretion by eESCs stimulated by NK cells contributes to the induction of macrophage recruitment and is thus implicated in the development of endometriosis.