Strategies of neutrophil diversification

Palomino‐Segura, Miguel; Sicilia, Jon; Ballesteros, Iván; Hidalgo, Andrés

doi:10.1038/s41590-023-01452-x

Cited by 47 publications

(29 citation statements)

References 104 publications

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“…Currently, the traditional concept that neutrophils comprise terminally differentiated cells with limited plasticity and highly conserved function has been critically revised ( 5, 6 ). Several studies support that during inflammatory conditions, the transition of mature neutrophils from bone marrow to the bloodstream is accompanied by changes at the transcriptional level that enable the acquisition of distinct functions within the affected tissues ( 5, 6 ). Previous clinical and experimental studies suggested that in the context of different inflammatory disorders, neutrophils may acquire differential plasticity which may be reflected by the NETs that they release ( 9, 10 ).…”

Section: Discussionmentioning

confidence: 99%

“…Cellular plasticity is fundamental to human immunity and, as recently recognized, a key aspect of neutrophil biology (5,6). Recent studies suggest that circulating neutrophils, as an adaptation to the different environmental conditions, undergo transcriptional reprogramming that allows them to acquire disease-specific phenotypes and commit their cell-fate plasticity upon their entrance to the site of tissue inflammation attracted by tissue-derived chemotactic factors (6). Activated neutrophils release a plethora of antimicrobial and proinflammatory mediators on extracellular vesicles and traps that could dictate their diverse functional role in different diseases (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

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Neutrophil-fibroblast crosstalk drives immunofibrosis in Crohn’s disease through IFNα pathway

Gavriilidis,

Divolis,

Natsi

et al. 2023

Preprint

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Crohn’s disease (CD) is characterized by chronic inflammation and intestinal fibrosis leading to lifelong complications. However, disease pathogenesis is elusive and the therapeutic options are limited. We investigated the interaction between neutrophils and intestinal fibroblasts in the development of CD immunofibrosis. Peripheral neutrophils, enriched neutrophil extracellular traps (eNETs), serum, primary intestinal fibroblasts (PIFs) and intestinal biopsies from CD and ulcerative colitis (UC) patients, and healthy individuals (HI), were studied. Neutrophil-targeted transcriptomics, multi-cytokine profiling and cell-based functional assays at mRNA/protein level were performed. Compared to UC, PIFs from CD patients displayed a distinct fibrotic phenotype characterized by negative Krüppel-like Factor-2 (KLF2) and increased cellular communication network factor-2 (CCN2) expression leading to collagen production. In UC and CD, PIFs-derived IL-8 appears as a culprit chemoattractant of neutrophils in the intestine, where CD neutrophils were accumulated close to fibrotic lesions. Functionally, only CD neutrophilsviaeNETs can induce a CD-like phenotype in HI PIFs, suggesting their fibrotic plasticity. High IFNα in serum and IFΝ-responsive signature in peripheral neutrophils were observed in CD, distinguishing it from UC. Moreover, CD serum can stimulate the release of fibrogenic eNETs from neutrophils in an IFNα-dependent manner, suggesting the priming role of IFNα in circulating neutrophils. Inhibition of eNETs or JAK signaling in neutrophils or PIFs prevented the neutrophil-mediated fibrotic effect on PIFs. Furthermore, serum IFNα and transcripts of key IFN-signaling components in neutrophils were well-correlated with CD severity. This study reveals the important role of IFNα/neutrophil/fibroblast axis in CD immunofibrosis, suggesting candidate biomarkers and putative therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neutrophil-fibroblast crosstalk drives immunofibrosis in Crohn’s disease through IFNα pathway

Gavriilidis,

Divolis,

Natsi

et al. 2023

Preprint

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“…Indeed, a growing number of studies have demonstrated the heterogeneity and plasticity of neutrophils. It has been reported that circulating and tissue neutrophils displayed substantial heterogeneity, in terms of phenotype, maturation\activation states and effector functions, due to circadian oscillations, aging, and the presence of microenvironment cues ( 3 , 8 , 70 ). Accordingly, freshly released and aged neutrophils showed considerable diversity in their repertoire of chemokines, PRRs, adhesion molecules, granule proteins, and in their ability to release NETs ( 46 , 71 – 73 ).…”

Section: Neutrophil Functional Heterogeneitymentioning

confidence: 99%

“…This hypothesis has been challenged by recent discoveries made possible by new technologies. For instance, the lifespan and heterogeneity of neutrophils have been re-evaluated in the last years ( 3 – 8 ).…”

Section: Introductionmentioning

confidence: 99%

Neutrophil diversity in inflammation and cancer

et al. 2023

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Neutrophils are the most abundant circulating leukocytes in humans and the first immune cells recruited at the site of inflammation. Classically perceived as short-lived effector cells with limited plasticity and diversity, neutrophils are now recognized as highly heterogenous immune cells, which can adapt to various environmental cues. In addition to playing a central role in the host defence, neutrophils are involved in pathological contexts such as inflammatory diseases and cancer. The prevalence of neutrophils in these conditions is usually associated with detrimental inflammatory responses and poor clinical outcomes. However, a beneficial role for neutrophils is emerging in several pathological contexts, including in cancer. Here we will review the current knowledge of neutrophil biology and heterogeneity in steady state and during inflammation, with a focus on the opposing roles of neutrophils in different pathological contexts.

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“…Additionally, marked heterogeneity is observed between circulating and tissue‐resident neutrophils. [ 197,198 ] Current endeavors are focused on establishing protocols to differentiate various stem cells into functionally active neutrophils that can aid in future research, especially genetic studies.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Dying to Defend: Neutrophil Death Pathways and their Implications in Immunity

Tu,

Ren,

Jiang

et al. 2023

Advanced Science

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Neutrophils, accounting for ≈70% of human peripheral leukocytes, are key cells countering bacterial and fungal infections. Neutrophil homeostasis involves a balance between cell maturation, migration, aging, and eventual death. Neutrophils undergo different death pathways depending on their interactions with microbes and external environmental cues. Neutrophil death has significant physiological implications and leads to distinct immunological outcomes. This review discusses the multifarious neutrophil death pathways, including apoptosis, NETosis, pyroptosis, necroptosis, and ferroptosis, and outlines their effects on immune responses and disease progression. Understanding the multifaceted aspects of neutrophil death, the intersections among signaling pathways and ramifications of immunity will help facilitate the development of novel therapeutic methods.

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Strategies of neutrophil diversification

Cited by 47 publications

References 104 publications

Neutrophil-fibroblast crosstalk drives immunofibrosis in Crohn’s disease through IFNα pathway

Neutrophil-fibroblast crosstalk drives immunofibrosis in Crohn’s disease through IFNα pathway

Neutrophil diversity in inflammation and cancer

Dying to Defend: Neutrophil Death Pathways and their Implications in Immunity

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