TNF-α and IL-10 Control CXCL13 Expression in Human Macrophages
TNF-α and IL-10 Control CXCL13 Expression in Human Macrophages
复制标题
DOI：
10.4049/jimmunol.1900790
复制
发表时间：
2020-05-01
影响因子：
4.4
通讯作者：
Vernhet, Laurent
中科院分区：
文献类型：
--
作者：
Bellamri, Nessrine;Viel, Roselyne;Vernhet, Laurent
趋化因子CXCL13控制着继发性淋巴组织的正常组织和非淋巴器官（尤其是肺）异位淋巴结构的新生。特发性肺纤维化（IPF）是一种致命且不可逆的间质性肺疾病，其进展和严重程度可通过循环血液中CXCL13的浓度来预测。虽然CXCL13是由肺组织产生的，但尚未确定哪些细胞参与其中。本研究探讨了IPF患者肺组织巨噬细胞产生CXCL13，以及人肺泡巨噬细胞（AM）和单核细胞源性巨噬细胞（MoDM）中控制CXCL13基因表达的信号通路。在IPF患者的CD68-和cd206阳性AM中发现CXCL13基因，当LPS刺激这些巨噬细胞和MoDM时，CXCL13基因被诱导。我们发现tnf - α和IL-10分别通过激活NF-kappa B和JAK/STAT通路调控MoDM和AM中CXCL13基因的最佳表达。我们还发现，IPF患者血液中tnf - α和CXCL13浓度显著相关，表明tnf - α有助于人类CXCL13的产生。总之，本研究结果表明来自IPF患者的AM产生CXCL13，并且NF-kappa B和JAK/STAT通路需要诱导该主要趋化因子的表达。
The chemokine CXCL13 controls the normal organization of secondary lymphoid tissues and the neogenesis of ectopic lymphoid structures in nonlymphoid organs, particularly the lungs. The progression and severity of idiopathic pulmonary fibrosis (IPF), a fatal and irreversible interstitial lung disease, is predicted by the circulating blood concentrations of CXCL13. Although CXCL13 is produced by pulmonary tissues, it has not been determined which cells are involved. This study examines CXCL13 production by lung tissue macrophages from patients with IPF and the signaling pathways controlling CXCL13 gene expression in human alveolar macrophages (AM) and monocyte-derived macrophages (MoDM). CXCL13 is found in CD68- and CD206-positive AM from patients with IPF, and the CXCL13 gene is induced in these macrophages and MoDM when they are stimulated with LPS. We found that TNF-alpha and IL-10 control optimal CXCL13 gene expression in MoDM and possibly in AM by activating the NF-kappa B and JAK/STAT pathways, respectively. We also found that blood TNF-alpha and CXCL13 concentrations are significantly correlated in patients with IPF, suggesting that TNF-alpha contributes to CXCL13 production in humans. In conclusion, the results of this study demonstrate that AM from patients with IPF produces CXCL13 and that the NF-kappa B and JAK/STAT pathways are required to induce the expression of this major chemokine.