Characterization and biological significance of IL-23-induced neutrophil polarization

Yang, Li; Zhu, Linnan; Chu, Zhulang; Yang, Tao; Sun, Hai‐Xi; Yang, Fan; Wang, Wei; Hou, Yuzhu; Wang, Peng; Zhao, Qingjie; Tao, Yaling; Zhang, Lianfeng; Zhang, Xiaodong; Zhao, Yong

doi:10.1038/cmi.2017.39

Cited by 33 publications

(41 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The recruitment and function of neutrophils is orchestrated differently within specific organs, depending on tissue-resident cells and the immune environment. [38][39][40] Notably, we observed that liver neutrophils were likely to exhibit an immunosuppressive phenotype as characterized by surface CD62 dim expression, especially at the immune contraction stage in viral infection (Supplementary Figure S2). Further evidence showed that neutrophils in the liver expressed higher levels of CXCL2, iNOS, Arg-1 and IL-10 than those in the spleen.…”

Section: Discussionmentioning

confidence: 89%

IL-33 induces immunosuppressive neutrophils via a type 2 innate lymphoid cell/IL-13/STAT6 axis and protects the liver against injury in LCMV infection-induced viral hepatitis

Liang

Yuan

et al. 2018

Cell Mol Immunol

View full text Add to dashboard Cite

Viral hepatitis is still a public health problem affecting several million people around the world. Neutrophils are polymorphonuclear cells that have a critical role in antibacterial infection. However, the role of neutrophils in viral infection is not fully understood. By using a mouse model of lymphocytic choriomeningitis virus infection-induced viral hepatitis, we observed increased neutrophil recruitment in the liver accompanied by enhanced CD8 T-cell responses. Liver neutrophils expressed high levels of immunomodulatory cytokines, such as C-X-C chemokine ligand 2, arginase-1, inducible nitric oxide synthase and interleukin (IL)-10, demonstrating immunosuppressive properties. Depletion of neutrophils in vivo by a neutralizing antibody resulted in the exacerbation of liver injury and the promotion of T-cell responses at the immune contraction stage. IL-33 significantly induced neutrophil recruitment in the liver and attenuated liver injury by limiting effector T-cell accumulation. Mechanistically, we found that IL-33 promoted the expression of arginase-1 in neutrophils through the type 2 innate lymphoid cell (ILC2)-derived IL-13. Additionally, IL-13 increased the inhibitory effect of neutrophils on CD8 T-cell proliferation in vitro, partially through arginase-1. Finally, we found that IL-13 induced arginase-1 expression, depending on signal transducer and activator of transcription factor 6 (STAT6) signaling. Therefore, IL-33 induced immunosuppressive neutrophils via an ILC2/IL-13/STAT6 axis. Collectively, our findings shed new light on the mechanisms associated with IL-33-triggered neutrophils in the liver and suggest potential targets for therapeutic investigation in viral hepatitis.Cellular and Molecular Immunology advance online publication, 5 February 2018; doi:10.1038/cmi.2017.147.

show abstract

Section: Discussionmentioning

confidence: 89%

IL-33 induces immunosuppressive neutrophils via a type 2 innate lymphoid cell/IL-13/STAT6 axis and protects the liver against injury in LCMV infection-induced viral hepatitis

Liang

Yuan

et al. 2018

Cell Mol Immunol

View full text Add to dashboard Cite

show abstract

“…It was suggested that IL-23 regulates cytokine production by neutrophils during experimental mold infections [20,21]. Subsequent studies confirmed the requirement of IL-23 for IL-17 production by neutrophils [22,24]. Another study suggested that IL-23 induces osteoclast differentiation in the mouse macrophage cell line RAW264.7 via an IL-17-independent mechanism [23].…”

Section: Discussionmentioning

confidence: 94%

“…Furthermore, IL-23 has been shown to induce dermal inflammation and acanthosis in an IL-17-independent manner [18,19]. IL-23-mediated effects that are independent of T cells have also been reported [20][21][22][23][24].…”

mentioning

confidence: 94%

IL-23 supports host defense against systemic Candida albicans infection by ensuring myeloid cell survival

et al. 2019

View full text Add to dashboard Cite

The opportunistic fungal pathogen Candida albicans can cause invasive infections in susceptible hosts and the innate immune system, in particular myeloid cell-mediated immunity, is critical for rapid immune protection and host survival during systemic candidiasis. Using a mouse model of the human disease, we identified a novel role of IL-23 in antifungal defense. IL-23-deficient mice are highly susceptible to systemic infection with C. albicans. We found that this results from a drastic reduction in all subsets of myeloid cells in the infected kidney, which in turn leads to rapid fungal overgrowth and renal tissue injury. The loss in myeloid cells is not due to a defect in emergency myelopoiesis or the recruitment of newly generated cells to the site of infection but, rather, is a consequence of impaired survival of myeloid cells at the site of infection. In fact, the absence of a functional IL-23 pathway causes massive myeloid cell apoptosis upon C. albicans infection. Importantly, IL-23 protects myeloid cells from apoptosis independently of the IL-23-IL-17 immune axis and independently of lymphocytes and innate lymphoid cells. Instead, our results suggest that IL-23 acts in a partially autocrine but not cell-intrinsic manner within the myeloid compartment to promote host protection from systemic candidiasis. Collectively, our data highlight an unprecedented and non-canonical role of IL-23 in securing survival of myeloid cells, which is key for maintaining sufficient numbers of cells at the site of infection to ensure efficient host protection. Author summaryLinked to advances in medical technology and the resulting increase in the number of intensive care patients, nosocomial infections with Candida albicans are on the rise. In patients suffering from invasive candidiasis the innate immune response is typically severely impaired. Strengthening the innate immune system has become a promising approach complementing the use of antifungal drugs. Our findings identify an unexpected and IL-17-independent role of IL-23 that prevents rapid death of myeloid cells during PLOS Pathogens | https://doi.

show abstract

“…Microarray procedure was performed according to the manufacturer's instructions and previous reports. 16 R (version 3.0.2) was used to draw the heatmap of lineage-restricted genes. The fold changes were calculated as the ratio of the expression level in each cell type versus the second highest expression level in all cell types.…”

Section: Microarray Analysismentioning

confidence: 99%

“…15 Our recent results also reveal that IL-23activated neutrophils expresses a unique gene expression profile and participate in the pathological process of colitis. 16 The extracellular inducing factors, the intracellualr molecular regulatory networks, the phenotype characteristics and the biological significance of the polarized neutrophils urgently need to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Characterization and allergic role of IL-33-induced neutrophil polarization

et al. 2018

Self Cite

View full text Add to dashboard Cite

Neutrophils are involved in the pathogenesis of allergy. However, the contribution of the different functionally polarized neutrophils in allergy needs to be clarified. We sought to define the characteristics of interleukin (IL)-33-induced neutrophils and the involvement of this subset of polarized neutrophils in allergic pathogenesis. Freshly isolated neutrophils were treated with different cytokines and the cytokine expression levels were detected by real-time PCR. The gene expression profile of IL-33-induced neutrophils was determined by microarray assay. Adoptive transfer assay was used to investigate the function of IL-33-induced neutrophils in an ovalbumin (OVA)-induced allergic asthma model. IL-33-treated neutrophils selectively produced IL-4, IL-5, IL-9 and IL-13 (referred as to N(IL-33) cells) and displayed a distinctive gene expression profile in sharp contrast to resting and lipopolysaccharide (LPS)-treated neutrophils. IL-33-induced neutrophils expressed high Levels of IL-1R2 on cell surface, whereas resting and LPS-treated neutrophils did not, indicating IL-1R2 might be used as a biomarker for N(IL-33) cells. Importantly, N(IL-33) neutrophils exist in the lungs of OVA-induced allergic asthma mice. Adoptive transfer of N(IL-33) neutrophils significantly promotes the severity of the lung pathogenesis in this model. IL-33 induces neutrophil polarization through c-Jun N-terminal kinase- and nuclear factor-κB-dependent pathways. A previously unappreciated neutrophil polarization driven by IL-33 with unique cell surface markers and cytokine/chemokine-producing gene profile was defined. The newly identified N(IL-33) subpopulation may have significant contribution to IL-33-related pathogenesis.

show abstract

Characterization and biological significance of IL-23-induced neutrophil polarization

Cited by 33 publications

References 66 publications

IL-33 induces immunosuppressive neutrophils via a type 2 innate lymphoid cell/IL-13/STAT6 axis and protects the liver against injury in LCMV infection-induced viral hepatitis

IL-33 induces immunosuppressive neutrophils via a type 2 innate lymphoid cell/IL-13/STAT6 axis and protects the liver against injury in LCMV infection-induced viral hepatitis

IL-23 supports host defense against systemic Candida albicans infection by ensuring myeloid cell survival

Characterization and allergic role of IL-33-induced neutrophil polarization

Contact Info

Product

Resources

About