CD5L attenuates allergic airway inflammation by expanding CD11chigh alveolar macrophages and inhibiting NLRP3 inflammasome activation via HDAC2
CD5L attenuates allergic airway inflammation by expanding CD11chigh alveolar macrophages and inhibiting NLRP3 inflammasome activation via HDAC2
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CD5L通过HDAC2扩增CD11chigh肺泡巨噬细胞和抑制NLRP 3炎性小体激活减轻过敏性气道炎症
DOI：
10.1111/imm.13543
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发表时间：
2022-07
期刊：
影响因子：
6.4
通讯作者：
Danlin Weng;Song Gao;Hailan Shen;Shifei Yao;Qi Huang;Yanyu Zhang;Wenjie Huang;Yan Wang
中科院分区：
文献类型：
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作者：
Danlin Weng;Song Gao;Hailan Shen;Shifei Yao;Qi Huang;Yanyu Zhang;Wenjie Huang;Yan Wang
过敏性哮喘是一种以2型免疫应答为主的气道炎症性疾病，目前尚无根治性治疗方法。已知CD5样抗原（CD5L）与多种炎性疾病有关。然而，CD5L在过敏性哮喘中的作用仍不清楚。本研究采用重组CD 5L（rCD 5L）对小鼠进行屋尘螨（HDM）和卵清蛋白（OVA）攻击，以探讨CD 5L在过敏性哮喘中的作用，并进一步探讨其可能机制。与PBS组比较，哮喘小鼠血清CD5L水平显著降低，肺组织和支气管肺泡灌洗液（BALF）中CD5L水平显著升高。CD5L降低哮喘小鼠气道炎症和Th2免疫应答。CD5L通过增加CD11chigh肺泡巨噬细胞（CD11chigh AM）发挥其抗炎作用，CD11chigh AM在过敏性哮喘中的抗炎作用通过CD11chigh AM耗竭和转移试验得到证实。此外，CD5L通过增加哮喘小鼠肺组织中HDAC 2的表达来增加CD5L+巨噬细胞并抑制NLRP 3炎性体活化。因此，我们的研究表明，CD5L在哮喘治疗中具有潜在的用途。
Allergic asthma is an airway inflammatory disease dominated by type 2 immune responses and there is currently no curative therapy for asthma. CD5‐like antigen (CD5L) has been known to be involved in a variety of inflammatory diseases. However, the role of CD5L in allergic asthma remains unclear. In the present study, mice were treated with recombinant CD5L (rCD5L) during house dust mite (HDM) and ovalbumin (OVA) challenge to determine the role of CD5L in allergic asthma, and the underlying mechanism was further explored. Compared with PBS group, serum CD5L levels of asthmatic mice were significantly decreased, and the levels of CD5L in lung tissues and bronchoalveolar lavage fluid (BALF) were significantly increased. CD5L reduced airway inflammation and Th2 immune responses in asthmatic mice. CD5L exerted its anti‐inflammatory function by increasing CD11chigh alveolar macrophages (CD11chigh AMs), and the anti‐inflammatory role of CD11chigh AMs in allergic asthma was confirmed by CD11chigh AMs depletion and transfer assays. In addition, CD5L increased the CD5L+ macrophages and inhibited NLRP3 inflammasome activation by increasing HDAC2 expression in lung tissues of asthmatic mice. Hence, our study implicates that CD5L has potential usefulness for asthma treatment.