Quantitative Analysis of OX62-Positive Dendritic Cell Distribution in the Rat Laryngeal Complex

Friedman, Aaron D.; Dan, Olivia; Drazba, Judith A.; Lorenz, Robert R.; Strome, Marshall

doi:10.1177/000348940711600610

Cited by 10 publications

(4 citation statements)

References 24 publications

(47 reference statements)

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“…The relatively new monoclonal antibody, OX62, 11 allows for more accurate identification of DC than MHC class I or II. Using this antibody, immunofluorescence, confocal microscopy, and computerized quantitation, our laboratory has confirmed that resting DC populations are up to 200 times more concentrated in the mucosa and submucosa compared with laryngotracheal sites distant to the airway lumen such as the parathyroid gland, thyroid gland, thyroartyenoid muscle, and supraglottic fat 12 . Based on this, analysis of the supraglottic, glottic, subglottic, and tracheal epithelium and subepithelium ensured identification of the majority of the donor DC at the time of transplantation.…”

Section: Introductionmentioning

confidence: 88%

Postallograft Donor and Recipient Dendritic Cell Trafficking in the Rat Larynx

et al. 2007

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The paradigm of donor DC efflux and recipient DC influx has been confirmed in a rat laryngeal transplant model, and the allograft-specific timing of these events has been elucidated. Similarities in total DC migration between allografts and isografts suggest that this phenomenon may not be driven entirely by major histocompatibility mismatch. Further understanding of trafficking may help with the goal of manipulating DC to induce allograft tolerance in the absence of generalized immunosuppression.

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Section: Introductionmentioning

confidence: 88%

Postallograft Donor and Recipient Dendritic Cell Trafficking in the Rat Larynx

et al. 2007

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“…Although an often overlooked anatomic subsite, the subglottis is uniquely enriched in antigen-presenting dendritic cells as well as T lymphocytes ( 39, 40 ). Additionally, it functions as a transition zone from the ciliated lining of the trachea to the squamous epithelium of the larynx.…”

Section: Disscussionmentioning

confidence: 99%

Idiopathic subglottic stenosis arises at the interface of host and pathogen

Gelbard

Shilts

Strickland

et al. 2022

Preprint

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Idiopathic subglottic stenosis (iSGS) is a rare fibrotic disease of the proximal airway affecting adult Caucasian women nearly exclusively. Life-threatening ventilatory obstruction occurs secondary to pernicious subglottic mucosal scar. Diverse diseases in divergent organ systems are associated with fibrosis, suggesting common biologic mechanisms. One well characterized pathway is chronic inflammation secondary to pathogen. In the present study, we explored the role of the proximal airway microbiome in iSGS pathogenesis. In human samples, abundant bacteria are detectable in iSGS scar as well as in health subglottic controls or patients that developed subglottic stenosis following endotracheal intubation. Interestingly, the community structure of the iSGS proximal airway microbiome does not appear disrupted. Rather, in iSGS defects in the airway epithelial barrier allow displacement of the native microbiome into the immunoprivileged lamina propria and are associated with adaptive immune activation. Animal models of iSGS confirm both bacteria and an adaptive immune response are necessary for pathologic proximal airway fibrosis. Single cell RNA sequencing of the affected airway in iSGS offers an unbiased characterization of the observed epithelial barrier dysfunction. The airway scar in iSGS patients demonstrates basal cell depletion and epithelial acquisition of a mesenchymal phenotype. The epithelial alterations are associated with the observed microbiome displacement, dysregulated immune activation, and localized fibrosis. These results refine our understanding of iSGS and implicate shared pathogenic mechanisms with distal airway fibrotic diseases.

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“…Cells were obtained from rat ipsilateral cervical lymph nodes and stained with the special marker OX62. 31 , 32 We found proportional increases in OX62 + DCs in rat ipsilateral cervical lymph nodes on postoperative day 12 ( Figs. 3 A, 3 B).…”

Section: Resultsmentioning

confidence: 66%

Topical Administration of 0.3% Tofacitinib Suppresses M1 Macrophage Polarization and Allograft Corneal Rejection by Blocking STAT1 Activation in the Rat Cornea

et al. 2022

Trans. Vis. Sci. Tech.

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Purpose M1 macrophages can promote corneal allograft rejection (CGR). Inhibiting M1 macrophage polarization by the JAK/STAT1 pathway may be a new strategy to prevent CGR. Tofacitinib, a potent pan-JAK inhibitor, can inhibit JAK/STAT activation. Here, we investigated the inhibitory effects of tofacitinib on M1 macrophage polarization and its therapeutic effect on rat CGR. Methods Corneal allograft transplantation was performed and administrated with 0.3% tofacitinib in rats. The corneal allografts were assessed clinically. The corneas were detected for M1 macrophages, lymphatic vessels, and inflammatory cytokine expression using immunohistochemistry and real-time polymerase chain reaction (PCR). Dendritic cells (DCs) in ipsilateral cervical lymph nodes were detected by flow cytometry. The effect and mechanism of tofacitinib on macrophages were explored by real-time PCR, enzyme-linked immunoassay, and western blot analysis in vitro. Results The results showed that topical administration of 0.3% tofacitinib significantly prolonged corneal graft survival. Tofacitinib-treated corneal allografts displayed a proportionate decrease in M1 macrophages and reduced lymphatic vessel density with fewer DCs in rat ipsilateral cervical lymph nodes. Tofacitinib reduced the mRNA expression of inflammatory cytokines, including iNOS, MCP-1, TNF-α, IL-6, IL-1β, and VEGF-C, and inhibited STAT1 activation in rat corneal grafts. In addition, tofacitinib suppressed M1 macrophage polarization via STAT1 activation after IFN-γ and lipopolysaccharide stimulation in vitro. Conclusions Tofacitinib could suppress M1 macrophage polarization and subsequently delay CGR by inhibiting STAT1 activation. The data indicate that tofacitinib is an effective drug for CGR. Translational Relevance This study provided evidence that topical administration of 0.3% tofacitinib may be a novel clinical strategy to prevent CGR.

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Quantitative Analysis of OX62-Positive Dendritic Cell Distribution in the Rat Laryngeal Complex

Cited by 10 publications

References 24 publications

Postallograft Donor and Recipient Dendritic Cell Trafficking in the Rat Larynx

Postallograft Donor and Recipient Dendritic Cell Trafficking in the Rat Larynx

Idiopathic subglottic stenosis arises at the interface of host and pathogen

Topical Administration of 0.3% Tofacitinib Suppresses M1 Macrophage Polarization and Allograft Corneal Rejection by Blocking STAT1 Activation in the Rat Cornea

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