(1) Background: Sarcoidosis is a chronic multisystem disorder of unknown aetiology, driven by a T-cell mechanism allowing T-cell attachment and transmigration through the endothelium, and endorsed by the expression of an integrin alpha-E beta-7 (CD103). This study aimed to analyse the different distribution and compartmentalisation of CD103 expression on T cell subsets in BAL, peripheral blood mononuclear cells (PBMC) and lymph nodes (LLN) from sarcoidosis patients. (2) Patients: We consecutively and prospectively enrolled 14 sarcoidosis patients. We collected PBMC, LLN and BAL at the same time from all patients. Through flow cytometric analysis, we analysed the expression of CD103 on regulatory and follicular T cell subsets. (3) Results: All patients were in radiological Scadding stage II. The multivariate analysis found that the variables which most influenced the peripheral blood compartment were high CD8+ and low ThReg, CD8+CD103+ and Tfh cell percentages. A principal component analysis plot performed to distinguish LLN, BAL and PBMC showed that they separated on the basis of CD4+, CD4+CD103+, CD8+, CD8+CD103+, TcEffector, TcNaive, ThNaive, ThEffector, Threg, ThregCD103+, Tfh, TcfCXC5+ and CD4+CD103+/CD4+ with 65.96% of the total variance. (4) Conclusions: Our study is the first to report a link between the imbalance in circulating, alveolar and lymph node CD8+ and CD8+CD103+ T cells, ThReg, Tfh and ThNaive and the CD103+CD4+/CD4+ T cell ratio in the development of sarcoidosis. These findings shine a spotlight on the pathogenesis of sarcoidosis and may offer new predictors for diagnosis. Our study provides additional understanding for a personalised, and hopefully more effective treatment of sarcoidosis.

Background Sarcoidosis features non-necrotizing granulomas consisting mainly of activated CD4-lymphocytes. T-cell activation is regulated by immune checkpoint (IC) molecules. The present study aimed to compare IC expression on CD4, CD8 and NK cells from peripheral, alveolar and lung-draining lymph node (LLN) samples of sarcoidosis patients. Methods Flow-cytometry analysis was performed to detect IC molecules and a regression decision tree model was constructed to investigate potential binary classifiers for sarcoidosis diagnosis as well as for the IC distribution. Results Fourteen patients (7 females) were consecutively recruited in the study; all enrolled patients showed hilo-mediastinal lymph node enlargement and lung parenchyma involvement with chest X-rays and high resolution computed tomography. CD4+PD1+ and CD8+PD1+ were higher in bronchoalveolar lavage (BAL) than in LLN (p = 0.0159 and p = 0.0439, respectively). CD4+ T-cell immunoglobulin and ITIM domain (TIGIT)+ were higher in BAL than in peripheral blood mononuclear cells (PBMCs) (p = 0.0239), while CD8+TIGIT+ were higher in PBMC than in BAL (p = 0.0386). CD56+TIGIT+ were higher in LLN than in PBMC (p = 0.0126). The decision-tree model showed the best clustering cells of PBMC, BAL and LLN: CD56, CD4/CD8 and CD4+TIGIT+ cells. Considering patients and controls, the best subset was CD4+CTLA-4+. Conclusion High expression of PD1 and TIGIT on T cells in BAL, as well as CTLA-4 and TIGIT on T cells in LLN, suggest that inhibition of these molecules could be a therapeutic strategy for avoiding the development of chronic inflammation and tissue damage in sarcoidosis patients. Miriana d'Alessandro & Laura Bergantini contributed equally to the study.

Bronchiolitis obliterans syndrome (BOS) is the most common form of CLAD and is characterized by airflow limitation and an obstructive spirometric pattern without high-resolution computed tomography (HRCT) evidence of parenchymal opacities. Computed tomography and microCT analysis show abundant small airway obstruction, starting from the fifth generation of airway branching and affecting up to 40–70% of airways. The pathogenesis of BOS remains unclear. It is a multifactorial syndrome that leads to pathological tissue changes and clinical manifestations. Because BOS is associated with the worst long-term survival in LTx patients, many studies are focused on the early identification of BOS. Markers may be useful for diagnosis and for understanding the molecular and immunological mechanisms involved in the onset of BOS. Diagnostic and predictive markers of BOS have also been investigated in various biological materials, such as blood, BAL, lung tissue and extracellular vesicles. The aim of this review was to evaluate the scientific literature on markers of BOS after lung transplant. We performed a systematic review to find all available data on potential prognostic and diagnostic markers of BOS.

No abstract

The present article aims to provide a comprehensive overview of the state of the art of legal science on crowdfunding and to lay the foundation for the understanding of some of its key concepts, facilitating the development of future legal research. This paper demonstrates that legal scholarship seems to not take full comparative advantage of the fact that many concerns are common across jurisdictions, such as encouraging SME development through access to risk capital or ensuring the protection of the unsophisticated investor. It also shows that scholarship and legislative efforts, predominantly in the US and the EU, are most often focused on investment crowdfunding and that these efforts usually attempt to define the obligations of the crowdfunding service provider, striking a balance between stimulating access to risk capital for start-ups and scaling up the crowdfunding business while, at the same time, protecting investors - in particular the unsophisticated ones. Even though it is challenging to legally define specific crowdfunding services, the commonly used typology of crowdfunding is found to be meaningful in a legal context, as it denotes the applicable legal framework. Considering that there is a correlation between the clarity of regulation in a country and the volume of crowdfunding, and given that crowdfunding is growing as both a method of finance and as a business, the time is ripe for legal scholars to direct their attention to the field. In doing so, they assist the actors in the market, the legislators, and the judiciary.