The Long Pentraxin PTX3 as a Link Between Innate Immunity, Tissue Remodeling, and Cancer

Doni, Andrea; Stravalaci, Matteo; Inforzato, Antonio; Magrini, Elena; Mantovani, Alberto; Garlanda, Cecília; Bottazzi, Barbara

doi:10.3389/fimmu.2019.00712

Cited by 124 publications

(112 citation statements)

References 143 publications

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“…Ptx3 itself, as well as other genes selective to Ptx3-LECs, have known or proposed roles in the extracellular matrix (ECM). PTX3 binds collagen and fibrinogen-domain containing proteins, including ECM components, but also other pattern recognition molecules like C1q and ficolins [60]; thus it may amplify innate pathogen recognition mechanisms as well as contributing to maintenance and repair of the LN medullary environment. The Ptx3-LEC marker Reelin ( Reln ) is an extracellular matrix glycoprotein.…”

Section: Resultsmentioning

confidence: 99%

A single-cell transcriptional roadmap of the mouse and human lymph node lymphatic vasculature

Xiang

Grosso

Pan

et al. 2020

Preprint

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Single-cell transcriptomics promises to revolutionize our understanding of the vasculature. Emerging computational methods applied to high dimensional single cell data allow integration of results between samples and species, and illuminate the diversity and underlying developmental and architectural organization of cell populations. Here, we illustrate these methods in analysis of mouse lymph node (LN) lymphatic endothelial cells (LEC) at single cell resolution. Clustering identifies five well-delineated subsets, including two medullary sinus subsets not recognized previously as distinct. Nearest neighbor alignments in trajectory space position the major subsets in a sequence that recapitulates known and suggests novel features of LN lymphatic organization, providing a transcriptional map of the lymphatic endothelial niches and of the transitions between them. Differences in gene expression reveal specialized programs for (1) subcapsular ceiling endothelial interactions with the capsule connective tissue and cells, (2) subcapsular floor regulation of lymph borne cell entry into the LN parenchyma and antigen presentation, and (3) medullary subset specialization for pathogen interactions and LN remodeling. LEC of the subcapsular sinus floor and medulla, which represent major sites of cell entry and exit from the LN parenchyma respectively, respond robustly to oxazolone inflammation challenge with enriched signaling pathways that converge on both innate and adaptive immune responses. Integration of mouse and human single-cell profiles reveals a conserved cross-species pattern of lymphatic vascular niches and gene expression, as well as specialized human subsets and genes unique to each species. The examples provided demonstrate the power of single-cell analysis in elucidating endothelial cell heterogeneity, vascular organization and endothelial cell responses. We discuss the findings from the perspective of LEC functions in relation to niche formations in the unique stromal and highly immunological environment of the LN.

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Section: Resultsmentioning

confidence: 99%

A single-cell transcriptional roadmap of the mouse and human lymph node lymphatic vasculature

Xiang

Grosso

Pan

et al. 2020

Preprint

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“…Finally, Ptx3, the gene encoding pentraxin 3, was highly upregulated after 2 ppm O3 exposure (FC 17.2). This gene belongs to a family of widely evolutionarily conserved proteins called pentraxins, among which are the acute phase proteins C-reactive protein (CRP) and its murine cognate serum amyloid component P (SAP) (DONI 2019). Ptx3 is less well characterized, but is induced by pro-inflammatory cytokines such as TNF, along with regulating chronic inflammation and responses to sterile tissue damage (KUNES et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional profiling of the murine airway response to acute ozone exposure

Tovar

Smith

Thomas

et al. 2019

Preprint

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Exposure to ambient ozone (O3) pollution causes airway inflammation, epithelial injury, and decreased lung function. Long-term exposure is associated with increased mortality and exacerbations of respiratory conditions. While the adverse health effects of O3 exposure have been thoroughly described, less is known about the molecular processes that drive these outcomes. The aim of this study was to describe the cellular and molecular alterations observed in murine airways after exposure to either 1 or 2 ppm O3. After exposing adult, female C57BL/6J mice to filtered air, 1 or 2 ppm O3 for 3 hours, we assessed hallmark responses including airway inflammatory cell counts, epithelial permeability, cytokine secretion, and morphological alterations of the large airways. Further, we performed RNA-seq to profile gene expression in two critical tissues involved in O3 responses: conducting airways (CA) and airway macrophages (AM). We observed a concentration-dependent increase in airway inflammation and injury, and a large number of genes were differentially expressed in both target tissues at both concentrations of O3. Genes that were differentially expressed in CA were generally associated with barrier function, detoxification processes, and cellular proliferation. The differentially expressed genes in AM were associated with innate immune signaling, cytokine production, and extracellular matrix remodeling. Overall, our study has described transcriptional responses to acute O3 exposure, revealing both shared and unique gene expression patterns across multiple concentrations of O3 and in two important O3-responsive tissues. These profiles provide broad mechanistic insight into pulmonary O3 toxicity, and reveal a variety of targets for refined followup studies.

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“…The constitutive expression of PTX3 is allowed by transcription binding factors, notably AP-1 and SP1, whose binding sites are located in its promoter (71). In addition, it contains the NFκB binding site and thus can be induced by several primary inflammatory signals, including TNFα and microbial components (72). In the CTL macrophages from the JD(+) cows, PTX3 was upregulated 26.7-fold ( Table 2) and lipids accumulated at a greater level in these cells (Figure 3) even though they were not infected.…”

Section: Lipid Homeostasismentioning

confidence: 99%

Transcriptome Profiling of Bovine Macrophages Infected by Mycobacterium avium spp. paratuberculosis Depicts Foam Cell and Innate Immune Tolerance Phenotypes

et al. 2020

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Mycobacterium avium spp. paratuberculosis (MAP) is the causative agent of Johne's disease (JD), also known as paratuberculosis, in ruminants. The mechanisms of JD pathogenesis are not fully understood, but it is known that MAP subverts the host immune system by using macrophages as its primary reservoir. MAP infection in macrophages is often studied in healthy cows or experimentally infected calves, but reports on macrophages from naturally infected cows are lacking. In our study, primary monocyte-derived macrophages (MDMs) from cows diagnosed as positive (+) or negative (-) for JD were challenged in vitro with live MAP. Analysis using nextgeneration RNA sequencing revealed that macrophages from JD(+) cows did not present a definite pattern of response to MAP infection. Interestingly, a considerable number of genes, up to 1436, were differentially expressed in JD(-) macrophages. The signatures of the infection time course of 1, 4, 8, and 24 h revealed differential expression of ARG2,

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The Long Pentraxin PTX3 as a Link Between Innate Immunity, Tissue Remodeling, and Cancer

Cited by 124 publications

References 143 publications

A single-cell transcriptional roadmap of the mouse and human lymph node lymphatic vasculature

A single-cell transcriptional roadmap of the mouse and human lymph node lymphatic vasculature

Transcriptional profiling of the murine airway response to acute ozone exposure

Transcriptome Profiling of Bovine Macrophages Infected by Mycobacterium avium spp. paratuberculosis Depicts Foam Cell and Innate Immune Tolerance Phenotypes

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