scholarly journals AB0693 TIM-3-EXPRESSING NEUTROPHILS AS A NOVEL INDICATOR TO ASSESS DISEASE ACTIVITY AND SEVERITY IN ANKYLOSING SPONDYLITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1641.1-1642
Author(s):  
X. Huang ◽  
T. Li ◽  
J. Chen ◽  
Y. Wang ◽  
S. Chen ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Clinical Manifestations ◽  
Chronic Inflammatory Disease ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Bacterial Killing ◽  
Markers Of Inflammation

Background:Ankylosing spondylitis (AS) is a type of chronic inflammatory disease that compromises the axial skeleton and sacroiliac joints. Many studies have shown that neutrophils play an important roles in the inflammatory process of AS. However, the immunomodulatory roles and mechanisms of neutrophils in AS are poorly understood. T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) has been reported as an important regulatory molecule, expressed and regulated on different innate immune cells, plays a pivotal role in several autoimmunity diseases. Recent study indicates that Tim3 is also expressed on neutrophils. However, the frequency and roles of Tim3-expressing neutrophils in AS was not clear.Objectives:In this study, we investigated the expression of Tim3 on neutrophils in AS patients and analyzed the correlation between the level of Tim3-expressing neutrophils and the disease activity of AS.Methods:AS Patients were recruited from Guangdong Second Provincial General Hospital (n=49). Age/sex-matched volunteers as Healthy controls (HC) (n=39). The medical history, clinical manifestations, physical examination, laboratory measurements were recorded. The expression of costimulatory molecules including programmed death 1 (PD-1), Tim-3 on neutrophils were determined by flow cytometry. The frequencies of Tim3-expressing neutrophils in AS patients were further analyzed for their correlation with markers of inflammation ESR and CRP, disease activity and severity of AS.Results:The expression of Tim3 on neutrophils in patients with AS was increased compared to the HC (Figure 1A). The frequency of Tim3-expressing neutrophils in patients with AS showed an positive correlation with ESR, CRP and ASAS-endorsed disease activity score (ASDAS) (Figure 1B). Moreover, the frequency of Tim3-expressing neutrophils in active patients(ASDAS≥1.3) was increased as compare with the inactive patients (ASDAS<1.3) (Figure 1C).Conclusion:Increased Tim-3 expression on neutrophils may be a novel indicator to assess disease activity and severity in AS, which may serves as a negative feedback mechanism preventing potential tissue damage caused by excessive inflammatory responses in AS patients.References:[1]Han, G., Chen, G., Shen, B. & Li, Y., Tim-3: an activation marker and activation limiter of innate immune cells.FRONT IMMUNOL4449 (2013).[2]Vega-Carrascal, I.et al., Galectin-9 signaling through TIM-3 is involved in neutrophil-mediated Gram-negative bacterial killing: an effect abrogated within the cystic fibrosis lung.J IMMUNOL1922418 (2014).Figure 1.(A)The expression of Tim3 on neutrophils in AS and HC.(B)The correction between Tim3-expressing neutrophils and ESR,CRP,ASDAS.(C) The expression of Tim3 on neutrophils in active and inactive patients.Disclosure of Interests:None declared

scholarly journals POS0369 ELEVATED EXPRESSION OF TIM-3 ON NEUTROPHILS CORRELATES WITH DISEASE ACTIVITY AND SEVERITY OF ANKYLOSING SPONDYLITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 414.2-415
Author(s):  
X. Huang ◽  
T. W. Li ◽  
J. Chen ◽  
Z. Huang ◽  
S. Chen ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Immune Cells ◽  
Clinical Manifestations ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Bacterial Killing ◽  
Markers Of Inflammation ◽  
Significant Difference

Background:Ankylosing spondylitis (AS) is a type of common, chronic inflammatory disease that compromises the axial skeleton and sacroiliac joints, causing inflammatory low back pain and progressive spinal stiffness, over time some patients develop spinal immobility and ankylosis which can lead to a decrease in quality of life. The last few decades, evidence has clearly indicated that neutrophil also plays key roles in the progression of AS. However, the immunomodulatory roles and mechanisms of neutrophils in AS are poorly understood. T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) has been reported as an important regulatory molecule, expressed and regulated on different innate immune cells, plays a pivotal role in several autoimmunity diseases. Recent study indicates that Tim3 is also expressed on neutrophils. However, the frequency and roles of Tim3-expressing neutrophils in AS was not clear.Objectives:In this study, we investigated the expression of Tim3 on neutrophils in AS patients and explored the correlation between the level of Tim3-expressing neutrophils and the disease activity and severity of AS.Methods:Patients with AS were recruited from Guangdong Second Provincial General Hospital (n=62). Age/sex-matched volunteers as Healthy controls (HC) (n=39). The medical history, clinical manifestations, physical examination, laboratory measurements were recorded. The expression of costimulatory molecules including programmed death 1 (PD-1), Tim-3 on neutrophils were determined by flow cytometry. The mRNA expression of PD-1 and Tim-3 was determined by real-time PCR. The levels of Tim3-expressing neutrophils in AS patients were further analyzed for their correlation with the markers of inflammation such as ESR,CRP,WBC and neutrophil count(NE), as well as disease activity and severity of AS. The expression of Tim3 on neutrophils was monitored during the course of treatment (4 weeks).Results:The expression of Tim3 on neutrophils in patients with AS was increased compared to the HC (Figure 1A). However, significant difference was observed in the frequency of PD-1-expressing neutrophils between AS patients and HC (Figure 1B). The expression analysis of Tim-3 mRNA, but not PD-1, confirmed the results obtained from flow cytometry (Figure 1C). The level of Tim3-expressing neutrophils in patients with AS showed an positive correlation with ESR, CRP and ASAS-endorsed disease activity score (ASDAS) (Figure 1D). Moreover, the frequency of Tim3-expressing neutrophils in active patients(ASDAS≥1.3) was increased as compare with the inactive patients (ASDAS<1.3) (Figure 1E). As shown in Figure 1F, the frequency of Tim3-expressing neutrophils decreased after the treatment.Conclusion:Increased Tim-3 expression on neutrophils may be a novel indicator to assess disease activity and severity in AS, which may serves as a negative feedback mechanism preventing potential tissue damage caused by excessive inflammatory responses in AS patients.References:[1]Han, G., Chen, G., Shen, B. & Li, Y., Tim-3: an activation marker and activation limiter of innate immune cells. FRONT IMMUNOL 4 449 (2013).[2]Vega-Carrascal, I. et al., Galectin-9 signaling through TIM-3 is involved in neutrophil-mediated Gram-negative bacterial killing: an effect abrogated within the cystic fibrosis lung. J IMMUNOL 192 2418 (2014).Figure 1.(A,B)The expression of Tim3 and PD-1 on neutrophils in AS and HC were determined by flow cytometry.(C) The expression of Tim3 and PD-1 on neutrophils in AS and HC were determined by RT-PCR.(D)The correction between Tim3-expressing neutrophils and ESR,CRP,ASDAS.(E) The expression of Tim3 on neutrophils in active and inactive patients.(F) Influence of treatment on the frequency of Tim3-expressing neutrophils.Disclosure of Interests:None declared

scholarly journals Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

2020 ◽  
Author(s):  
Abigail Elliot ◽  
Henna Myllymäki ◽  
Yi Feng
Keyword(s):  
Immune Cells ◽  
Cancer Biology ◽  
Inflammatory Responses ◽  
Live Imaging ◽  
Innate Immune ◽  
Leukocyte Recruitment ◽  
Innate Immune Cells ◽  
Neoplastic Cells ◽  
Tumour Development ◽  
Tumour Initiation

The zebrafish is now an important model organism for cancer biology studies and provides some unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level thus providing novel insights into our understanding of cancer. Here we summarise and discuss available transgenic zebrafish tumour models and what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response toward transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour associated macrophages and neutrophils in mammalian models and present evidence which supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to signals mediating leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

scholarly journals Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1018 ◽  
Author(s):  
Abigail Elliot ◽  
Henna Myllymäki ◽  
Yi Feng
Keyword(s):  
Immune Cells ◽  
Cancer Biology ◽  
Inflammatory Responses ◽  
Live Imaging ◽  
Innate Immune ◽  
Leukocyte Recruitment ◽  
Innate Immune Cells ◽  
Neoplastic Cells ◽  
Tumour Development ◽  
Tumour Initiation

The zebrafish is now an important model organism for cancer biology studies and provides unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level, providing novel insights into our understanding of cancer. Here we summarise the available transgenic zebrafish tumour models and discuss what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response towards transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour-associated macrophages and neutrophils in mammalian models and present evidence that supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to the signals that mediate leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells in zebrafish appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

scholarly journals A lectin that targets specific bacteria for killing on DNA-based extracellular traps

2020 ◽  
Author(s):  
Timothy Farinholt ◽  
Christopher Dinh ◽  
Adam Kuspa
Keyword(s):  
Dictyostelium Discoideum ◽  
Immune Cells ◽  
Binding Proteins ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Bacterial Killing ◽  
Extracellular Traps ◽  
Bacterial Binding ◽  
Binding Lectin ◽  
Dna Scaffold

AbstractAnimal defenses directed against bacteria include DNA-based extracellular traps (ETs) that are produced by innate immune cells. ET-bound bacteria are prevented from further tissue dissemination and are eventually killed by ET-bound antibacterial proteins. It is unclear how bacteria bind to ETs, though it has been proposed that the negatively-charged DNA scaffold of the ETs is involved. We have found that the bacterial-binding lectin CadA is a component of the ETs produced by the innate immune cells of Dictyostelium discoideum and is required for the binding and killing of two Enterobacteriaceae by ETs, but not other bacteria. Our results suggest that ETs selectively sequester bacteria and that lectins can facilitate bacterial killing by acting as ET-bacteria binding proteins.

Cytokine release from innate immune cells: association with diverse membrane trafficking pathways

Blood ◽  
2011 ◽  
Vol 118 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Paige Lacy ◽  
Jennifer L. Stow
Keyword(s):  
Membrane Trafficking ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Cytokine Release ◽  
Research Findings ◽  
Specific Receptors ◽  
Different Cell Types

AbstractCytokines released from innate immune cells play key roles in the regulation of the immune response. These intercellular messengers are the source of soluble regulatory signals that initiate and constrain inflammatory responses to pathogens and injury. Although numerous studies describe detailed signaling pathways induced by cytokines and their specific receptors, there is little information on the mechanisms that control the release of cytokines from different cell types. Indeed, the pathways, molecules, and mechanisms of cytokine release remain a “black box” in immunology. Here, we review research findings and new approaches that have begun to generate information on cytokine trafficking and release by innate immune cells in response to inflammatory or infectious stimuli. Surprisingly complex machinery, multiple organelles, and specialized membrane domains exist in these cells to ensure the selective, temporal, and often polarized release of cytokines in innate immunity.

scholarly journals Host–Microbe Interactions and Gut Health in Poultry—Focus on Innate Responses

2019 ◽  
Vol 7 (5) ◽  
pp. 139 ◽  
Author(s):  
Leon J. Broom
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Gut Health ◽  
Mucosal Surfaces ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Commercial poultry are continually exposed to, frequently pathogenic, microorganisms, usually via mucosal surfaces such as the intestinal mucosa. Thus, understanding host–microbe interactions is vital. Many of these microorganisms may have no or limited contact with the host, while most of those interacting more meaningfully with the host will be dealt with by the innate immune response. Fundamentally, poultry have evolved to have immune responses that are generally appropriate and adequate for their acquired microbiomes, although this is challenged by commercial production practices. Innate immune cells and their functions, encompassing inflammatory responses, create the context for neutralising the stimulus and initiating resolution. Dysregulated inflammatory responses can be detrimental but, being a highly conserved biological process, inflammation is critical for host defence. Heterogeneity and functional plasticity of innate immune cells is underappreciated and offers the potential for (gut) health interventions, perhaps including exogenous opportunities to influence immune cell metabolism and thus function. New approaches could focus on identifying and enhancing decisive but less harmful immune processes, improving the efficiency of innate immune cells (e.g., targeted, efficient microbial killing) and promoting phenotypes that drive resolution of inflammation. Breeding strategies and suitable exogenous interventions offer potential solutions to enhance poultry gut health, performance and welfare.

scholarly journals The Impact of Nanoparticles on Innate Immune Activation by Live Bacteria

2020 ◽  
Vol 21 (24) ◽  
pp. 9695
Author(s):  
Benjamin J. Swartzwelter ◽  
Alexandra C. Fux ◽  
Litty Johnson ◽  
Elmer Swart ◽  
Sabine Hofer ◽  
...  
Keyword(s):  
Immune Cells ◽  
Inflammatory Responses ◽  
Particle Surface ◽  
Modern Technology ◽  
Innate Immune ◽  
Engineered Nanoparticles ◽  
Immune Memory ◽  
Innate Immune Cells ◽  
Live Bacteria ◽  
The Impact

The innate immune system evolved to detect and react against potential dangers such as bacteria, viruses, and environmental particles. The advent of modern technology has exposed innate immune cells, such as monocytes, macrophages, and dendritic cells, to a relatively novel type of particulate matter, i.e., engineered nanoparticles. Nanoparticles are not inherently pathogenic, and yet cases have been described in which specific nanoparticle types can either induce innate/inflammatory responses or modulate the activity of activated innate cells. Many of these studies rely upon activation by agonists of toll-like receptors, such as lipopolysaccharide or peptidoglycan, instead of the more realistic stimulation by whole live organisms. In this review we examine and discuss the effects of nanoparticles on innate immune cells activated by live bacteria. We focus in particular on how nanoparticles may interfere with bacterial processes in the context of innate activation, and confine our scope to the effects due to particles themselves, rather than to molecules adsorbed on the particle surface. Finally, we examine the long-lasting consequences of coexposure to nanoparticles and bacteria, in terms of potential microbiome alterations and innate immune memory, and address nanoparticle-based vaccine strategies against bacterial infection.

scholarly journals Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Kathleen L. McCoy
Keyword(s):  
Pattern Recognition ◽  
Immune Cells ◽  
Innate Immune System ◽  
Cannabinoid Receptors ◽  
Inflammatory Responses ◽  
Endocannabinoid System ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Toll Like Receptor ◽  
Receptor Family

Since the discovery of the endocannabinoid system consisting of cannabinoid receptors, endogenous ligands, and biosynthetic and metabolizing enzymes, interest has been renewed in investigating the promise of cannabinoids as therapeutic agents. Abundant evidence indicates that cannabinoids modulate immune responses. An inflammatory response is triggered when innate immune cells receive a danger signal provided by pathogen- or damage-associated molecular patterns engaging pattern-recognition receptors. Toll-like receptor family members are prominent pattern-recognition receptors expressed on innate immune cells. Cannabinoids suppress Toll-like receptor-mediated inflammatory responses. However, the relationship between the endocannabinoid system and innate immune system may not be one-sided. Innate immune cells express cannabinoid receptors and produce endogenous cannabinoids. Hence, innate immune cells may play a role in regulating endocannabinoid homeostasis, and, in turn, the endocannabinoid system modulates local inflammatory responses. Studies designed to probe the interaction between the innate immune system and the endocannabinoid system may identify new potential molecular targets in developing therapeutic strategies for chronic inflammatory diseases. This review discusses the endocannabinoid system and Toll-like receptor family and evaluates the interaction between them.

scholarly journals LPS Induces Opposing Memory-like Inflammatory Responses in Mouse Bone Marrow Neutrophils

2021 ◽  
Vol 22 (18) ◽  
pp. 9803
Author(s):  
Trim Lajqi ◽  
Maylis Braun ◽  
Simon Alexander Kranig ◽  
David Frommhold ◽  
Johannes Pöschl ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
In Vivo Studies ◽  
Mouse Bone Marrow ◽  
Innate Immune Cells ◽  
Trained Immunity

A growing body of evidence suggests that innate immune cells can respond in a memory-like (adaptive) fashion, which is referred to as trained immunity. Only few in vivo studies have shown training effects in neutrophils; however, no in vitro setup has been established to study the induction of trained immunity or tolerance in neutrophils by microbial agents. In light of their short lifespan (up to 48 h), we suggest to use the term trained sensitivity for neutrophils in an in vitro setting. Here, we firstly describe a feasible two-hit model, using different doses of lipopolysaccharide (LPS) in bone marrow neutrophils. We found that low doses (10 pg/mL) induce pro-inflammatory activation (trained sensitivity), whereas priming with high doses (100 ng/mL) leads to suppression of pro-inflammatory mediators such as TNF-α or IL-6 (tolerance) (p < 0.05). On a functional level, trained neutrophils displayed increased phagocytic activity and LFA-1 expression as well as migrational capacity and CD11a expression, whereas tolerant neutrophils show contrasting effects in vitro. Mechanistically, TLR4/MyD88/PI3Ks regulate the activation of p65, which controls memory-like responses in mouse bone marrow neutrophils (p < 0.05). Our results open a new window for further in vitro studies on memory-like inflammatory responses of short-lived innate immune cells such as neutrophils.

scholarly journals The Regulation of Inflammation by Innate and Adaptive Lymphocytes

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
David Alex Cronkite ◽  
Tara M. Strutt
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
T And B Cells ◽  
Cell Functions ◽  
Past Experiences

Inflammation plays an essential role in the control of pathogens and in shaping the ensuing adaptive immune responses. Traditionally, innate immunity has been described as a rapid response triggered through generic and nonspecific means that by definition lacks the ability to remember. Recently, it has become clear that some innate immune cells are epigenetically reprogrammed or “imprinted” by past experiences. These “trained” innate immune cells display altered inflammatory responses upon subsequent pathogen encounter. Remembrance of past pathogen encounters has classically been attributed to cohorts of antigen-specific memory T and B cells following the resolution of infection. During recall responses, memory T and B cells quickly respond by proliferating, producing effector cytokines, and performing various effector functions. An often-overlooked effector function of memory CD4 and CD8 T cells is the promotion of an inflammatory milieu at the initial site of infection that mirrors the primary encounter. This memory-conditioned inflammatory response, in conjunction with other secondary effector T cell functions, results in better control and more rapid resolution of both infection and the associated tissue pathology. Recent advancements in our understanding of inflammatory triggers, imprinting of the innate immune responses, and the role of T cell memory in regulating inflammation are discussed.

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