picrosirius-red-staining-for-semiquantitative-histopathologic

Picrosirius Red Staining for Semiquantitative Histopathologic Evaluation of Collagen Deposition in Murine Models of Chronic Lung Allograft Rejection

Fibrosis is the pathophysiologic hallmark of chronic rejection after lung transplantation and the foremost hurdle to long-term recipient survival. Several ...

University of Freiburg

Allograft rejection remains the major hurdle in lung transplantation despite modern immunosuppressive treatment. As part of the alloreactive process, B cells are increasingly recognized as modulators of alloimmunity and initiators of a donor-specific humoral response. In chronically rejected lung allografts, B cells contribute to the formation of tertiary lymphoid structures and promote local alloimmune responses. However, B cells are functionally heterogeneous and some B cell subsets may promote alloimmune tolerance. In this review, we describe the current understanding of B-cell-dependent mechanisms in pulmonary allograft rejection and highlight promising future strategies that employ B cell-targeted therapies.

B Cell Immunity in Lung Transplant Rejection - Effector Mechanisms and Therapeutic Implications.

Cluster of differentiation 26 (CD26)/dipeptidyl peptidase 4 (DPP4) is an exopeptidase that is expressed as a transmembrane protein in many organs but also present in a circulating soluble form. Beyond its enzymatic and costimulatory activity, CD26/DPP4 is involved in the pathogenesis of chronic fibrotic diseases across many organ types, such as liver cirrhosis, kidney fibrosis and lung fibrosis. Organ fibrosis is associated with a high morbidity and mortality, and there are no causative therapies that can effectively attenuate the progress of the disease. Growing evidence suggests that inhibiting CD26/DPP4 can modulate the profibrotic tissue microenvironment and thus reduce fibrotic changes within affected organs. This review summarizes the role of CD26/DPP4 in fibroproliferative disorders and highlights new opportunities for an antifibrotic treatment by CD26/DPP4 inhibition. As a major advantage, CD26/DPP4 inhibitors have been in safe and routine clinical use in type 2 diabetes for many years and thus qualify for repurposing to repurpose as a promising therapeutic against fibrosis. LINKED ARTICLES: This article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc.

Targeting cluster of differentiation 26 / dipeptidyl peptidase 4 (CD26/DPP4) in organ fibrosis.

Thymic epithelial tumors (TETs) are rare thoracic malignancies with a favorable prognosis when complete surgical resection can be achieved. Therapeutic options for advanced, irresectable, or recurrent disease are limited and currently, a therapeutic standard treatment beyond platinum-based chemotherapy is undefined. Immune checkpoint inhibitors are effective against TETs, however their use is associated with a serious risk of immune-mediated toxicity. In this article, we highlight new insights regarding markers of predictive value for both treatment efficacy and risk of adverse effects in immune checkpoint inhibitor treatment for thymic epithelial tumors.

Balancing the Risk of Adverse Events against the Efficacy of Immunotherapy in Advanced Thymic Epithelial Tumors.

The transplantation model provides the opportunity to assess the relevance of a molecule of interest for tumor cell extravasation by using a respective genetically modified donor animal. Here, we present a protocol for orthotopic single-lung transplantation in mice as a tool for lung metastasis studies. We describe steps for animal preparation, lung transplantation, and tumor cell injection. We then detail procedures for the direct comparison of tumor cell spreading between the genetically modified left lung and the naive right lung parenchyma. For complete details on the use and execution of this protocol, please refer to Giannou et al. (2023)..

Article	Year
B Cell Immunity in Lung Transplant Rejection - Effector Mechanisms and Therapeutic Implications. Frontiers in immunology\| PubMed ID: 35320934	2022
Targeting cluster of differentiation 26 / dipeptidyl peptidase 4 (CD26/DPP4) in organ fibrosis. British journal of pharmacology\| PubMed ID: 36196001	2023
Balancing the Risk of Adverse Events against the Efficacy of Immunotherapy in Advanced Thymic Epithelial Tumors. Cancers\| PubMed ID: 36612283	2022
Protocol for orthotopic single-lung transplantation in mice as a tool for lung metastasis studies. STAR protocols\| PubMed ID: 37950863	2023
Repeated Single-lung Transplantation After Previous Contralateral Pneumonectomy-A Unique Challenge. Transplantation direct\| PubMed ID: 38481965	2024

Birte Ohm

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