I-Cheng Ho’s research while affiliated with Brigham and Women's Hospital and other places

What is this page?


This page lists works of an author who doesn't have a ResearchGate profile or hasn't added the works to their profile yet. It is automatically generated from public (personal) data to further our legitimate goal of comprehensive and accurate scientific recordkeeping. If you are this author and want this page removed, please let us know.

Publications (95)


Figure 1. Characterization of iNKT cell effector subsets in GATA-3 FF and FFcre mice. iNKT cells of indicated genotypes in the thymus (A), spleen (B), and lymph node (C) were identified with TCR and loaded CD1d tetramer, and then further divided into iNKT1, iNKT2, and iNKT17 sublineages based on the expression of PLZF, RORγt, and T-bet. The numbers of total iNKT cells and iNKT1/iNKT2/iNKT17 subsets from thymus, spleen and lymph nodes of GATA-3fl/fl (FF) and GATA3fl/fl Cd4-cre mice (FFcre) were calculated and statistical analyses were performed with Student's two-tailed t-test. (D) The expression levels of PLZF, RORγt, and T-bet of GATA-3 FF and FFcre thymic iNKT cells were quantified with FACS and are shown by histogram. (E) Representative
Figure 2. The iNKT effector lineage differentiation in GATA-3 FFcre mice is altered. Thymocytes of FF and FFcre mice were stimulated for 2 h in vitro with PMA and ionomycin. The production of IFNγ, IL-4, IL-13, IL-17, GM-CSF, and Granzyme B by thymic iNKT cells was then analyzed with intracellular cytokine staining. Representative FACS plots are shown in (A). Cumulative data from at least 3 mice are shown in (B).
Figure 3. Single-cell RNA sequencing revealed the difference in functional subsets between GATA-3 FF and FFcre iNKT cells. (A) Thymic iNKT cells from GATA-3 FF and FFcre mice were sorted and subjected to RNA-based next-generation sequencing (RNA-seq). Transcriptomic analysis was performed using the 10× Genomics platform. Uniform Manifold Approximation and Projection (UMAP) dimensionality reduction analysis showed six major clusters. (B) The dot plot shows the expression and distribution of selected genes across the iNKT cell subpopulation. (C) UMAP plots (left panel) depict the distribution of iNKT subsets from FF and FFcre, while corresponding percentages are displayed in the right panel.
Figure 4. Predictive developmental trajectories of iNKT thymocytes in GATA3 FF and FFcre mice. (A) Partition-based Graph Abstraction (PAGA) analysis was applied to the single-cell RNA sequencing data obtained from GATA-3 FF and FFcre iNKT thymocytes. The PAGA graph (right panel) and
Figure 7. Overexpression of ICOS rescues iNKT2 and iNKT17 cells of GATA-3-deficient mice. (A) The thymocytes and splenocytes from GATA-3 FF and FFcre mice were stained with TCRβ, CD4, CD8, CD44, CD62L, NK1.1, loaded CD1d tetramer, CD127, and ICOS. The histogram plots show the surface expression levels of CD127 and ICOS on thymic iNKT cells (TCRβ + tetramer + ), CD8 singlepositive thymocyte (TCRβ hi CD4 − CD8 + ), splenic naïve (TCRβ + CD4 − CD8 + CD44 − CD62L + ), and activated/memory (TCRβ + CD4 − CD8 + CD44 hi CD62L − ) CD8 T cells. (B) The gating strategy for identifying iNKT17 and iNKT2 cells from FFcre thymocytes overexpressing ICOS and CD127 via retroviral transduction is illustrated. Cumulative results are presented in the lower panel. (two-sided unpaired t-test, ns, *p < 0.05, **p < 0.01)
ScRNA-seq Analyses Define the Role of GATA3 in iNKT Cell Effector Lineage Differentiation
  • Article
  • Full-text available

June 2024

·

41 Reads

Cells

Tzong-Shyuan Tai

·

·

Wan-Chu Chuang

·

[...]

·

While the transcription factor GATA-3 is well-established for its crucial role in T cell development, its specific influence on invariant natural killer T (iNKT) cells remains relatively unexplored. Using flow cytometry and single-cell transcriptomic analysis, we demonstrated that GATA-3 deficiency in mice leads to the absence of iNKT2 and iNKT17 cell subsets, as well as an altered distribution of iNKT1 cells. Thymic iNKT cells lacking GATA-3 exhibited diminished expression of PLZF and T-bet, key transcription factors involved in iNKT cell differentiation, and reduced production of Th2, Th17, and cytotoxic effector molecules. Single-cell transcriptomics revealed a comprehensive absence of iNKT17 cells, a substantial reduction in iNKT2 cells, and an increase in iNKT1 cells in GATA-3-deficient thymi. Differential expression analysis highlighted the regulatory role of GATA-3 in T cell activation signaling and altered expression of genes critical for iNKT cell differentiation, such as Icos, Cd127, Eomes, and Zbtb16. Notably, restoration of Icos, but not Cd127, expression could rescue iNKT cell development in GATA-3-deficient mice. In conclusion, our study demonstrates the pivotal role of GATA-3 in orchestrating iNKT cell effector lineage differentiation through the regulation of T cell activation pathways and Icos expression, providing insights into the molecular mechanisms governing iNKT cell development and function.

Download

Peptidylarginine deiminase 2 citrullinates MZB1 and promotes the secretion of IgM and IgA

November 2023

·

50 Reads

·

2 Citations

Introduction MZB1 is an endoplasmic reticulum residential protein preferentially expressed in plasma cells, marginal zone and B1 B cells. Recent studies on murine B cells show that it interacts with the tail piece of IgM and IgA heavy chain and promotes the secretion of these two classes of immunoglobulin. However, its role in primary human B cells has yet to be determined and how its function is regulated is still unknown. The conversion of peptidylarginine to peptidylcitrulline, also known as citrullination, by peptidylarginine deiminases (PADs) can critically influence the function of proteins in immune cells, such as neutrophils and T cells; however, the role of PADs in B cells remains to be elucidated. Method An unbiased analysis of human lung citrullinome was conducted to identify citrullinated proteins that are enriched in several chronic lung diseases, including rheumatoid arthritis-associated interstitial lung disease (RA-ILD), chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis, compared to healthy controls. Mass spectrometry, site-specific mutagenesis, and western blotting were used to confirm the citrullination of candidate proteins. Their citrullination was suppressed by pharmacological inhibition or genetic ablation of PAD2 and the impact of their citrullination on the function and differentiation of human B cells was examined with enzyme-linked immunosorbent assay, flow cytometry, and co-immunoprecipitation. Results Citrullinated MZB1 was preferentially enriched in RA-ILD but not in other chronic lung diseases. MZB1 was a substrate of PAD2 and was citrullinated during the differentiation of human plasmablasts. Ablation or pharmacological inhibition of PAD2 in primary human B cells attenuated the secretion of IgM and IgA but not IgG or the differentiation of IgM or IgA-expressing plasmablasts, recapitulating the effect of ablating MZB1. Furthermore, the physical interaction between endogenous MZB1 and IgM/IgA was attenuated by pharmacological inhibition of PAD2. Discussion Our data confirm the function of MZB1 in primary human plasmablasts and suggest that PAD2 promotes IgM/IgA secretion by citrullinating MZB1, thereby contributing to the pathogenesis of rheumatoid arthritis and RA-ILD.


Citrullination of matrisomal proteins in health and diseases

October 2023

·

33 Reads

·

2 Citations

Proteins once translated are subjected to post-translational modifications (PTMs) that can critically modify their characteristics. Citrullination is a unique type of PTM that is catalysed by peptidylarginine deiminase (PAD) enzymes, which regulate a multitude of physiological functions such as apoptosis, gene expression and immune response by altering the structure and function of cellular proteins. However, emerging data have unravelled compelling evidence to support that PAD-mediated citrullination is not exclusive to cellular proteins; rather citrullination of extracellular matrix (ECM) proteins also plays a major contributing role in various physiological/pathological conditions. Here, we discuss putative mechanisms for citrullination-induced alterations in the function of ECM proteins. Further, we put emphasis on influential roles of ECM citrullination in various pathological scenarios to underscore the clinical potential of its manipulation in human diseases. This article is part of the Theo Murphy meeting issue ‘The virtues and vices of protein citrullination’.


Figure 3. Transcriptomic analyses of Ets1KO iNKT cells. Stage 0 iNKT cells from Het and Ets1KO mice were sorted and subjected to RNA-based next-generation sequencing (RNA-seq). (A) The enrichment map shows the significantly suppressed functions in KO compared with Het stage 0 Figure 3. Transcriptomic analyses of Ets1KO iNKT cells. Stage 0 iNKT cells from Het and Ets1KO mice were sorted and subjected to RNA-based next-generation sequencing (RNA-seq). (A) The enrichment map shows the significantly suppressed functions in KO compared with Het stage 0 iNKT cells. Nodes are GO gene sets, and edges indicate shared genes between GO gene sets. Node size represents the number of perturbed genes in a given set. (B,C) Differences in various genes' expression in Het and KO stage 0 iNKT cells are shown in a volcano plot (B) and a heat map (C). p-value < 0.05 was used to identify differentially expressed genes in the volcano plot. The heat map represents data from two independent RNA-seq. (D) The results of GSEA analyses of NKT differentiation signatures (upper panel) and NKT activation signature (lower panel) of Het and KO stage 0 iNKT cells are shown.
Figure 4. Partial rescue of the differentiation of Ets1KO iNKT cells with a Vα14Jα18 TCR transgene. (A) The result of GSEA analysis of the TCR signaling pathway is shown. (B) The surface level of TCR and CD5 in thymic iNKT cells of indicated genotypes was compared in the histogram. (C) Representative NK1.1/CD44 plots of splenic iNKT cells of indicated genotypes are shown. The percentages of stage 1 and stage 2 splenic iNKT cells from six pairs of TG/KO and TG/Het mice are shown in the right panel. (D,E) The percentage and absolute numbers of total, CD4+, and CD4− iNKT cells in spleens (D) and livers (E) of indicated genotypes are shown. Representative CD4/CD44 FACS plots of splenic iNKT cells of indicated genotypes are also shown in (D).
Figure 5. Identification of ICOS as a target gene of Ets1. (A) cDNA was prepared from various thymic iNKT subpopulations of indicated genotypes, and the transcript levels of ICOS were quantified with quantitative PCR. (B,C) The surface levels of ICOS in different stages of thymic iNKT cells (B) and peripheral iNKT cells (C) are shown. (D) Activated Th cells were subjected to ChIP analysis using anti-Ets1 or control IgG. The recruitment of Ets1 to the promoter of ICOS, CD127, and TLR7 was examined with quantitative PCR. (E,F). Bone marrow cells transduced with RV vector
Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZF

November 2021

·

47 Reads

·

3 Citations

International Journal of Molecular Sciences

The transcription factor Ets1 is essential for the development/differentiation of invariant Natural Killer T (iNKT) cells at multiple stages. However, its mechanisms of action and target genes in iNKT cells are still elusive. Here, we show that Ets1 is required for the optimal expression of the Vα14Jα18 T cell receptor (TCR) in post-selected thymic iNKT cells and their immediate differentiation. Ets1 is also critical for maintaining the peripheral homeostasis of iNKT cells, which is a role independent of the expression of the Vα14Jα18 TCR. Genome-wide transcriptomic analyses of post-selected iNKT cells further reveal that Ets1 controls leukocytes activation, proliferation differentiation, and leukocyte-mediated immunity. In addition, Ets1 regulates the expression of ICOS and PLZF in iNKT cells. More importantly, restoring the expression of PLZF and the Vα14Jα18 TCR partially rescues the differentiation of iNKT cells in the absence of Ets1. Taken together, our results establish a detailed molecular picture of how Ets1 regulates the stepwise differentiation of iNKT cells.


Differential impacts of TNFα inhibitors on the transcriptome of Th cells

July 2021

·

55 Reads

·

4 Citations

Arthritis Research & Therapy

Background Targeting TNFα is beneficial in many autoimmune and inflammatory diseases, including rheumatoid arthritis. However, the response to each of the existing TNFα inhibitors (TNFis) can be patient- and/or disease-dependent. In addition, TNFis can induce the production of type 1 interferons (IFNs), which contribute to their non-infection side effects, such as pustular psoriasis. Thus far, the molecular mechanisms mediating the drug-specific effects of TNFis and their induction of type 1 IFNs are not fully understood. Methods Peripheral blood mononuclear cells (PBMCs) were collected from healthy donors and stimulated in vitro with anti-CD3 and anti-CD28 in the absence or presence of adalimumab, etanercept, or certolizumab. Th cells were isolated from the stimulated PBMCs, and their RNA was subjected to RNA-seq and quantitative polymerase chain reaction. Results Adalimumab and etanercept, which contain Fc, but not certolizumab, which does not contain Fc, inhibited the expression of several effector cytokines by Th cells within anti-CD3/anti-CD28-stimulated PBMCs. Transcriptomic analyses further showed that adalimumab, but not certolizumab, reciprocally induced type 1 IFN signals and the expression of CD96 and SIRPG in Th cells. The unique effects of adalimumab were not due to preferential neutralization of soluble TNFα but instead were mediated by several distinct mechanisms independent or dependent of Fc-facilitated physical interaction between Th cells and CD14+ monocytes. Conclusions TNFis can have drug-specific effects on the transcriptional profile of Th cells.


PAD2-mediated citrullination of Fibulin-5 promotes elastogenesis

July 2021

·

59 Reads

·

12 Citations

Matrix Biology

The formation of elastic fibers is active only in the perinatal period. How elastogenesis is developmentally regulated is not fully understood. Citrullination is a unique form of post-translational modification catalyzed by peptidylarginine deiminases (PADs), including PAD1-4. Its physiological role is largely unknown. By using an unbiased proteomic approach of lung tissues, we discovered that FBLN5 and LTBP4, two key elastogenic proteins, were temporally modified in mouse and human lungs. We further demonstrated that PAD2 citrullinated FBLN5 preferentially in young lungs compared to adult lungs. Genetic ablation of PAD2 resulted in attenuated elastogenesis in vitro and age-dependent emphysema in vivo. Mechanistically, citrullination protected FBLN5 from proteolysis and subsequent inactivation of its elastogenic activity. Furthermore, citrullinated but not native FBLN5 partially rescued in vitro elastogenesis in the absence of PAD activity. Our data uncover a novel function of citrullination, namely promoting elastogenesis, and provide additional insights to how elastogenesis is regulated.


Predicting response to etanercept (Eta) and adalimumab (Ada) in patients with rheumatoid arthritis. A, Schematic diagram of the Reversal of PTPN22 gene Signature (REPS) assay. Pretreatment peripheral blood mononuclear cells (PBMCs) from Treatments Against RA and Effects on ¹⁸F‐fluorodeoxyglucose–positron emission tomography/computed tomography Trial (TARGET) subjects were subjected to the REPS assay. The cells were harvested 24 hours later. Some samples were analyzed with fluorescence‐activated cell sorting. B, Left, Representative forward scatter (FSC)/side scatter (SSC) plot of samples from the Central Pain in Rheumatoid Arthritis (CPIRA) study and the TARGET study. Right, Percentage of cells in the live cell gate for each sample. The transcript level of PTPN22 in all samples was analyzed with quantitative polymerase chain reaction. C, Fold change in PTPN22 expression in patients treated with etanercept and patients treated with adalimumab, grouped together. D, Analysis of the results shown in C using an area under the receiver operating characteristic curve. E and F, Fold change in PTPN22 expression in patients treated with etanercept (E) and patients treated with adalimumab (F). In B, C, E, and F, horizontal lines and error bars show the mean ± SEM; symbols represent individual patients. P values were determined by Mann‐Whitney 1‐tailed test. TNFi = tumor necrosis factor inhibitors; AUC = area under the curve; 95% CI = 95% confidence interval; R = responders; NR = nonresponders.
Validation of a Bioassay for Predicting Response to Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis

April 2021

·

107 Reads

·

2 Citations

While the five current FDA‐approved classes of targeted disease modifying anti‐rheumatic drugs (DMARDs) have comparable efficacy in rheumatoid arthritis (RA), the response of an individual patient to each targeted DMARD can vary widely even among drugs within the same class. Thus far, there is no biomarker or assay in routine clinical practice for predicting a patient’s response in a drug‐specific or even class‐specific manner (1).



Reciprocal regulation of Th2 and Th17 cells by PAD2-mediated citrullination

November 2019

·

41 Reads

·

37 Citations

JCI Insight

Dysregulated citrullination, a unique form of posttranslational modification catalyzed by the peptidylarginine deiminases (PADs), has been observed in several human diseases, including rheumatoid arthritis. However, the physiological roles of PADs in the immune system are still poorly understood. Here, we report that global inhibition of citrullination enhances the differentiation of type 2 helper T (Th2) cells but attenuates the differentiation of Th17 cells, thereby increasing the susceptibility to allergic airway inflammation. This effect on Th cells is due to inhibition of PAD2 but not PAD4. Mechanistically, PAD2 directly citrullinates GATA3 and RORγt, 2 key transcription factors determining the fate of differentiating Th cells. Citrullination of R330 of GATA3 weakens its DNA binding ability, whereas citrullination of 4 arginine residues of RORγt strengthens its DNA binding. Finally, PAD2-deficient mice also display altered Th2/Th17 immune response and heightened sensitivity to allergic airway inflammation. Thus, our data highlight the potential and caveat of PAD2 as a therapeutic target of Th cell-mediated diseases.


ALDH7A1 inhibits the intracellular transport pathways during hypoxia and starvation to promote cellular energy homeostasis

September 2019

·

144 Reads

·

18 Citations

The aldehyde dehydrogenase (ALDH) family of metabolic enzymes converts aldehydes to carboxylates. Here, we find that the reductive consequence of ALDH7A1 activity, which generates NADH (nicotinamide adenine dinucleotide, reduced form) from NAD, underlies how ALDH7A1 coordinates a broad inhibition of the intracellular transport pathways. Studying vesicle formation by the Coat Protein I (COPI) complex, we elucidate that NADH generated by ALDH7A1 targets Brefeldin-A ADP-Ribosylated Substrate (BARS) to inhibit COPI vesicle fission. Moreover, defining a physiologic role for the broad transport inhibition exerted by ALDH7A1, we find that it acts to reduce energy consumption during hypoxia and starvation to promote cellular energy homeostasis. These findings advance the understanding of intracellular transport by revealing how the coordination of multiple pathways can be achieved, and also defining circumstances when such coordination is needed, as well as uncovering an unexpected way that NADH acts in cellular energetics.


Citations (73)


... Furthermore, MZB1 belongs to the family of endoplasmic reticulum (ER) chaperone proteins that regulate both surface expression and secretion of IgM [44][45][46]. MZB1 also seems to play a crucial role in the regulation of mitochondrial function, cell apoptosis, and calcium homeostasis [47,48].Through the comprehensive integration and validation of transcriptomic and proteomic data, alongside immunohistochemical analyses, we propose that MZB1 is a protein integral to B cell development and antibody production. Its upregulation in PD indicates potential immune dysregulation in this context, suggesting that MZB1 may serve as a promising biomarker for PD [49]. ...

Reference:

Identification of core genes related to exosomes and screening of potential targets in periodontitis using transcriptome profiling at the single-cell level
Peptidylarginine deiminase 2 citrullinates MZB1 and promotes the secretion of IgM and IgA

... The two studies mentioned above, which suggest a role for PADI4 in heart development and demonstrate a non-cellautonomous role in heart fibrosis, both report that loss of PADI4 leads to the reduction of genes associated with the ECM (Singh et al. [7]; Van Bruggen et al. [11]). Additionally, an excellent review by Saifi & Ho, details the current knowledge on the mechanisms and functions associated with citrullination of matrisomal proteins [12]. The authors focus in particular on how aberrant citrullination of such proteins may impact disease development and the clinical potential of manipulating ECM protein citrullination. ...

Citrullination of matrisomal proteins in health and diseases

... To assess the immunological effects of APOC2 K70 mutations on tumor immune microenvironment of lung cancer, we established APOC2 Sh rescue -WT and -K70R murine lung cancer cell lines (LLC cells) (Figure 6A). Peripheral blood mononuclear cells (PBMCs) [41] from healthy individuals were co-cultured with APOPC2-WT or -K70R cancer cells ( Figure 6B). After coculturing with APOPC2-WT cells, flow cytometry analysis showed a significant increase in the frequency of CD4 + FOXP3 + Tregs and a decrease in the frequency of CD8 + effector T cells compared to co-culturing with APOPC2-K70R cells ( Figure 6C). ...

Differential impacts of TNFα inhibitors on the transcriptome of Th cells

Arthritis Research & Therapy

... The cells were treated with the pan-PAD inhibitor BB-Cl-amidine trifluoroacetate (SML2250-25MG; Sigma) for 48 hours at a concentration of 500 nM, twice, at 24-hour intervals, alone or following TGFВ activation. The culture plates were harvested for specific experiments after treatment completion as described below [22,23]. ...

PAD2-mediated citrullination of Fibulin-5 promotes elastogenesis
  • Citing Article
  • July 2021

Matrix Biology

... With this background, numerous efforts have been reported to predict the efficacy of TNFi in advance. These efforts have included serum proteins, single-nucleotide polymorphisms (SNPs), peripheral blood gene expressions, peripheral blood epigenomic status, peripheral blood immune cell populations (analyzed by flow cytometry), synovial histology, and comprehensive synovial gene analysis [8][9][10][11][12][13][14][15][16][17][18][19]. However, access to these advanced technologies may be limited to certain countries and advanced facilities due to cost, labor requirements, and the need for process standardization. ...

Validation of a Bioassay for Predicting Response to Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis

... Ets1 is expressed at relatively high levels in all stages of iNKT cells. Germline deficiency of Ets1 results in a near absence of iNKT cells, making it challenging to study the roles and mechanisms of action of Ets1 in regulating iNKT cell biology [20,32]. ...

Ets1 regulates the differentiation and function of iNKT cells through both Pointed domain-dependent and domain-independent mechanisms
  • Citing Article
  • March 2020

Cellular & Molecular Immunology

... ; https://doi.org/10.1101/2024.06.30.601403 doi: bioRxiv preprint 4 an optimal NET-targeted therapeutic approach should aim to mitigate the detrimental 67 effects of NETs while preserving or enhancing virus-specific immunity. 68 While NET targeting may improve clinical outcomes led by the infection [14], its effects 69 on adaptive immune responses against SARS-CoV-2 remain unclear. We analyzed CC-BY-ND 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. ...

Reciprocal regulation of Th2 and Th17 cells by PAD2-mediated citrullination
  • Citing Article
  • November 2019

JCI Insight

... This effect may be a normal, physiological role of Aβ40, of which multiple have been reported (Plant et al., 2003;Theda et al., 2016;Lennol et al., 2021). Other mitochondrial proteins delta-1-pyrroline-5-carboxylate dehydrogenase mitochondrial, methylmalonate-semialdehyde dehydrogenase [acylating] mitochondrial, alpha-aminoadipic semialdehyde dehydrogenase, alpha-aminoadipic semialdehyde synthase mitochondrial and lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex mitochondrial, which are involved in enzymes of mitochondrial complexes (Ahn et al., 2015;Yang et al., 2019;Holmes, 2023;Su et al., 2024), were decreased by Aβ40 and increased by dexamethasone. This highlights that Aβ40 and dexamethasone can both have suppressive and promoting effects on mitochondrial protein expression, which may relate to the specific roles of each protein. ...

ALDH7A1 inhibits the intracellular transport pathways during hypoxia and starvation to promote cellular energy homeostasis

... This gene signature can be partially replicated by TNFα or CD28 signalling pathways and abolished in vitro with adalimumab, etanercept or tocilizumab. This in vitro reversal may be utilised to predict clinical responsiveness to targeted therapy (189,190). Disease sitetargeted RNA interference system was established by creating a non-viral compound between shRNA against TACE (shTNF-α converting enzyme ) and a bone resorption site-specific peptide carrier made up of aspartate and arginine repeating sequences (191). The shTACE/peptide carrier combination reduced arthritic symptoms in collagen-induced arthritis (CIA) animals by improving anti-inflammatory and anti-osteoclastogenic properties. ...

Utilizing a PTPN22 gene signature to predict response to targeted therapies in rheumatoid arthritis
  • Citing Article
  • April 2019

Journal of Autoimmunity

... Several lines of evidence indicate that tumor-associated neutrophils are important players in cancer progression [12,13]. More recently, it has been proposed that neutrophils may influence the tumor properties through the release of neutrophil extracellular traps (NETs) [14][15][16][17]. Primarily described as an antimicrobial mechanism, NETs are composed of a double-stranded DNA decorated with neutrophil nuclear and granular proteins, such as citrullinated histones, myeloperoxidase, metalloproteinases, and elastase [18]. ...

Citrullination and Neutrophil Extracellular Traps
  • Citing Chapter
  • September 2017