B Cells Are Not Involved in the Regulation of Adenoviral TGF-β1– or Bleomycin-Induced Lung Fibrosis in Mice

Moog, Marie; Hinze, Christopher Alexander; Bormann, Tina; Aschenbrenner, Franziska; Knudsen, Lars; DeLuca, David S.; Jonigk, Danny; Welte, Tobias; Gauldie, Jack; Kolb, Martin; Maus, Ulrich A.

doi:10.4049/jimmunol.2100767

Cited by 7 publications

(5 citation statements)

References 76 publications

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“…Identification and quantification of macrophages and neutrophils recovered from BAL fluids and lung tissue of S . pneumoniae -infected WT and S100A9 KO mice was done by flow cytometric analysis as described previously [ 44 , 81 , 86 ]. Briefly, S .…”

Section: Methodsmentioning

confidence: 99%

S100A9 is indispensable for survival of pneumococcal pneumonia in mice

Ostermann,

Seeliger,

David

et al. 2023

PLoS Pathog

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S100A8/A9 has important immunomodulatory roles in antibacterial defense, but its relevance in focal pneumonia caused by Streptococcus pneumoniae (S. pneumoniae) is understudied. We show that S100A9 was significantly increased in BAL fluids of patients with bacterial but not viral pneumonia and correlated with procalcitonin and sequential organ failure assessment scores. Mice deficient in S100A9 exhibited drastically elevated Zn2+ levels in lungs, which led to bacterial outgrowth and significantly reduced survival. In addition, reduced survival of S100A9 KO mice was characterized by excessive release of neutrophil elastase, which resulted in degradation of opsonophagocytically important collectins surfactant proteins A and D. All of these features were attenuated in S. pneumoniae-challenged chimeric WT→S100A9 KO mice. Similarly, therapy of S. pneumoniae-infected S100A9 KO mice with a mutant S100A8/A9 protein showing increased half-life significantly decreased lung bacterial loads and lung injury. Collectively, S100A9 controls central antibacterial immune mechanisms of the lung with essential relevance to survival of pneumococcal pneumonia. Moreover, S100A9 appears to be a promising biomarker to distinguish patients with bacterial from those with viral pneumonia. Trial registration: Clinical Trials register (DRKS00000620).

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Section: Methodsmentioning

confidence: 99%

S100A9 is indispensable for survival of pneumococcal pneumonia in mice

Ostermann,

Seeliger,

David

et al. 2023

PLoS Pathog

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“…Infiltration of T cells, B cells, and macrophages in the lung tissue in response to bleomycin treatment has been observed, and their activation can contribute to the progression of fibrosis. [51][52][53] This infiltration leads to the release of pro-inflammatory mediators that eventually cause fibrosis, which is a major contributor to end-stage lung failure and death in many chronic cases. Release of cytokines such as TGF-β, IL-1, IL-6, and IL-13 has also been observed during the pro-fibrotic phenotype in damaged lungs.…”

Section: Mechanism Of Lung Injury Induced By Bleomycinmentioning

confidence: 99%

The Regenerative Power of Stem Cells: Treating Bleomycin-Induced Lung Fibrosis

Vats,

Chaturvedi

2023

SCCAA

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Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with no known cure, characterized by the formation of scar tissue in the lungs, leading to respiratory failure. Although the exact cause of IPF remains unclear, the condition is thought to result from a combination of genetic and environmental factors. One of the most widely used animal models to study IPF is the bleomycin-induced lung injury model in mice. In this model, the administration of the chemotherapeutic agent bleomycin causes pulmonary inflammation and fibrosis, which closely mimics the pathological features of human IPF. Numerous recent investigations have explored the functions of various categories of stem cells in the healing process of lung injury induced by bleomycin in mice, documenting the beneficial effects and challenges of this approach. Differentiation of stem cells into various cell types and their ability to modulate tissue microenvironment is an emerging aspect of the regenerative therapies. This review article aims to provide a comprehensive overview of the role of stem cells in repairing bleomycin-induced lung injury. It delves into the mechanisms through which various types of stem cells, including mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, and lung resident stem cells, exert their therapeutic effects in this specific model. We have also discussed the unique set of intermediate markers and signaling factors that can influence the proliferation and differentiation of alveolar epithelial cells both during lung repair and homeostasis. Finally, we highlight the challenges and opportunities associated with translating stem cell therapy to the clinic for IPF patients. The novelty and implications of this review extend beyond the understanding of the potential of stem cells in treating IPF to the broader field of regenerative medicine. We believe that the review paves the way for further advancements in stem cell therapies, offering hope for patients suffering from this debilitating and currently incurable disease.

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“…In autoimmune disease, B cells lose self-tolerance and generate pathogenic autoantibodies, which can lead to systemic organ dysfunction. B cells have been identified in lung parenchymal tissue adjacent to regions of fibrosis in different forms of ILD, including IPF, rheumatoid arthritis-associated ILD, SSc-ILD, and hypersensitivity pneumonitis [ 81 , 82 , 83 , 84 ]. Beyond the lung, there is evidence of interplay between B cells and adipose tissue, whereby B cells regulate the metabolic effects of excess adiposity, and adipose tissue alters B cell composition and function [ 85 ].…”

Section: Inflammation and Ildmentioning

confidence: 99%

Linking Adiposity to Interstitial Lung Disease: The Role of the Dysfunctional Adipocyte and Inflammation

Macklin,

Thompson,

Kawano-Dourado

et al. 2023

Cells

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Adipose tissue has functions beyond its principal functions in energy storage, including endocrine and immune functions. When faced with a surplus of energy, the functions of adipose tissue expand by mechanisms that can be both adaptive and detrimental. These detrimental adipose tissue functions can alter normal hormonal signaling and promote local and systemic inflammation with wide-ranging consequences. Although the mechanisms by which adipose tissue triggers metabolic dysfunction and local inflammation have been well described, little is known about the relationship between adiposity and the pathogenesis of chronic lung conditions, such as interstitial lung disease (ILD). In this review, we detail the conditions and mechanisms by which adipose tissue becomes dysfunctional and relate this dysfunction to inflammatory changes observed in various forms of ILD. Finally, we review the existing basic and clinical science literature linking adiposity to ILD, highlighting the need for additional research on the mechanisms of adipocyte-mediated inflammation in ILD and its clinical implications.

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B Cells Are Not Involved in the Regulation of Adenoviral TGF-β1– or Bleomycin-Induced Lung Fibrosis in Mice

Cited by 7 publications

References 76 publications

S100A9 is indispensable for survival of pneumococcal pneumonia in mice

S100A9 is indispensable for survival of pneumococcal pneumonia in mice

The Regenerative Power of Stem Cells: Treating Bleomycin-Induced Lung Fibrosis

Linking Adiposity to Interstitial Lung Disease: The Role of the Dysfunctional Adipocyte and Inflammation

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