Anti-F4/80 treatment attenuates Th2 cell responses: Implications for the role of lung interstitial macrophages in the asthmatic mice
Anti-F4/80 treatment attenuates Th2 cell responses: Implications for the role of lung interstitial macrophages in the asthmatic mice
复制标题
抗 F4/80 治疗减弱 Th2 细胞反应：对哮喘小鼠肺间质巨噬细胞作用的影响
DOI：
10.1016/j.intimp.2021.108009
复制
发表时间：
2021-07-24
影响因子：
5.6
通讯作者：
Nie, Hanxiang
中科院分区：
文献类型：
--
作者：
Deng, Nishan;Guo, Xuxue;Nie, Hanxiang
在卵清蛋白（OVA）诱导的哮喘小鼠中，肺间质巨噬细胞（IMs）可以极化为另一种激活表型。然而，在哮喘小鼠中，肺IMs的选择性激活在Th2细胞反应中的作用尚不清楚。在这里，我们利用抗f4 /80治疗，该治疗已被证明可以选择性地消耗小鼠中的IMs，并研究该治疗如何调节肺中Th2细胞的反应，以及这种调节是否依赖于哮喘小鼠模型中的肺IMs。研究表明，抗f4 /80治疗可减轻OVA或屋尘螨（HDM）免疫和攻击小鼠的Th2细胞反应。抗f4 /80治疗不针对ova诱导的哮喘小鼠的肺泡巨噬细胞（AMs），也不影响野生型小鼠中其他免疫细胞类型的丰度，包括B细胞、T细胞和NK细胞。然而，这种治疗确实抑制了ova诱导的哮喘小鼠肺组织中选择性活化巨噬细胞极化标记物的表达，包括精氨酸酶-1、m-1和Fizz-1。此外，我们发现抗f4 /80治疗对Th2细胞反应的抑制作用可以在肺IMs过继转移后逆转。综上所述，我们的数据表明，抗f4 /80治疗可减弱Th2细胞反应，这至少部分与哮喘小鼠模型中肺IMs的消耗有关。这表明靶向肺IMs可能为治疗哮喘提供一种潜在的治疗方案。
Lung interstitial macrophages (IMs) can be polarized towards an alternative activation phenotype in ovalbumin (OVA)-induced asthmatic mice. However, the role of alternative activation of lung IMs in Th2 cell responses in the asthmatic murine is still unclear. Here, we leverage an anti-F4/80 treatment which has been shown to selectively deplete IMs in mice and investigate how this treatment modulates Th2 cell responses in lung and whether the modulation is dependent on lung IMs in murine models of asthma. We show that anti-F4/80 treatment alleviates Th2 cell responses in mice immunized and challenged with OVA or house dust mite (HDM). The anti-F4/80 treatment does not target lung alveolar macrophages (AMs) in OVA-induced asthmatic mice or impact the abundance of other immune cell types, including B cells, T cells, and NK cells in wild-type mice. However, this treatment does inhibit the expression of polarized markers of alternatively activated macrophages, including arginase-1, Ym-1, and Fizz-1 in the lung tissues from OVA-induced asthmatic mice. Furthermore, we find that the inhibitory effects of anti-F4/80 treatment on Th2 cell responses can be reversed upon adoptive transfer of lung IMs. Taken together, our data show that anti-F4/80 treatment attenuates Th2 cell responses, which is at least partially related to depletion of lung IMs in murine models of asthma. This suggests that targeted lung IMs may provide a potential therapeutic protocol for the treatment of asthmatics.