The functional diversity of neutrophils and clustered polarization of immunity
The functional diversity of neutrophils and clustered polarization of immunity
复制标题
中性粒细胞的功能多样性与免疫的集群极化
DOI：
10.1038/s41423-020-0378-y
复制
发表时间：
2020
影响因子：
24.1
通讯作者：
Zhao Yong
中科院分区：
文献类型：
--
作者：
Xu Yanan;Zhang Qian;Zhao Yong
Neutrophils, bone marrow-derived innate immune cells, are among the first defensive and inflammatory responses of the host to infection and other danger signals. Increasing evidence indicates that neutrophils are critically involved in shaping adaptive immunity as professional antigen-presenting cells (APCs). 1–3 However, neutrophils also negatively regulate inflammatory and immune responses or promote tissue repair and wound healing through multiple approaches. 3–5 With the widely diverse roles of neutrophils in host homeostasis and diseases, it is necessary to identify new subsets of functionally different neutrophils. Interestingly and importantly, Li et al. 6 and Sun et al. 7 recently identified N (IL-23) and N (IL-33) subsets, respectively. These findings are of importance for us to fully understand the biological diversity of neutrophils and, even more importantly, could reveal the wider functional polarization of neutrophils beyond the traditional N1/N2 bidirectional polarization. Accumulating evidence has revealed that neutrophils exhibit considerable functional plasticity and diversity and that there may be distinct neutrophil subsets. Tsuda et al. reported that type 1 neutrophils (N1) with the CD49d+ CD11b− phenotype predominately produce IL-12 and CCL3, type 2 neutrophils (N2) display the CD49d− CD11b+ phenotype and mainly produce IL-10 and CCL2, and CD49d− CD11b− resting neutrophils (N0) have no significant cytokine and chemokine productions. 8 Tumor-associated neutrophils are proposed to display an antitumorigenic N1 phenotype versus a protumorigenic N2 phenotype. 9–11 N1 neutrophils express high levels of immune-activating cytokines and chemokines, low levels of arginase, and have a strong tumor cell-killing capability in vitro, presenting antitumor activity, whereas N2 neutrophils induced by TGF-β in tumors display a protumor phenotype. In contrast to circulating neutrophils, splenic neutrophils express B-cellstimulating factors, such as BAFF, APRIL, and IL-21, as well as B-cellattracting chemokines, such as CXCL12 and CXCL13, to promote immunoglobulin class switching, somatic hypermutation, and antibody production. 12 In recent studies reported by Li et al., after stimulation with more than ten cytokines, only IL-23 treatment promoted Th17-like neutrophil polarization (referred to as N (IL-23) cells); these neutrophils selectively produce IL-17A, IL-17F, and IL-22 at the mRNA and protein levels and displays a distinctive gene expression profile compared with those of N0 and LPS-treated neutrophils (referred to as N (LPS) cells). IL-23 induces N (IL-23) polarization via STAT3-dependent RORγt and BATF pathways. 6 Importantly, these N (IL-23) cells are detectable in DSS-induced colitis and are involved in the pathogenesis of DSS-induced colitis in an IL-17-dependent manner. 6 In contrast, IL-33 induces Th9-like neutrophil polarization (referred to as the N (IL-33) cell subset). 7 These N (IL-33) cells express and produce high levels of IL-9 and certain quantities of IL-4, IL-5, and IL-13 by activating c-Jun N-terminal kinase-and NF-κB-dependent pathways. 7 Compared with N0, N (LPS), and N (IL-23) cells, these N (IL-33) cells display a unique gene expression profile, as determined by RNA-seq assays 7 (unpublished data). Importantly, N (IL-33) neutrophils are found in the lungs of OVA-induced allergic inflammation mice, as detected by flow cytometry. The adoptive transfer of the induced N (IL-33) neutrophils markedly enhances the severity of the lung pathology in these allergic inflammation mice. 7 The discovery of functionally different neutrophil subsets, such as N (IL-23) and N (IL-33), in both in vitro and in vivo systems …
