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Renin is the key enzyme of the systemic renin–angiotensin–aldosterone system, which plays an essential role in regulating blood pressure and maintaining electrolyte and extracellular volume homeostasis. Renin is mainly produced and secreted by specialized juxtaglomerular (JG) cells in the kidney. In the present study, we report for the first time that the conserved transmembrane receptor neuropilin‐1 (NRP1) participates in the development of JG cells and plays a key role in renin production. We used the myelin protein zero‐Cre (P0‐Cre) to abrogate Nrp1 constitutively in P0‐Cre lineage‐labelled cells of the kidney. We found that the P0‐Cre precursor cells differentiate into renin‐producing JG cells. We employed a lineage‐tracing strategy combined with RNAscope quantification and metabolic studies to reveal a cell‐autonomous role for NRP1 in JG cell function. Nrp1‐deficient animals displayed abnormal levels of tissue renin expression and failed to adapt properly to a homeostatic challenge to sodium balance. These findings provide new insights into cell fate decisions and cellular plasticity operating in P0‐Cre–expressing precursors and identify NRP1 as a novel key regulator of JG cell maturation. Key points: Renin is a centrepiece of the renin–angiotensin–aldosterone system and is produced by specialized juxtaglomerular cells (JG) of the kidney.Neuropilin‐1 (NRP1) is a conserved membrane‐bound receptor that regulates vascular and neuronal development, cancer aggressiveness and fibrosis progression.We used conditional mutagenesis and lineage tracing to show that NRP1 is expressed in JG cells where it regulates their function.Cell‐specific Nrp1 knockout mice present with renin paucity in JG cells and struggle to adapt to a homeostatic challenge to sodium balance.The results support the versatility of renin‐producing cells in the kidney and may open new avenues for therapeutic approaches. [ABSTRACT FROM AUTHOR]

Acute kidney injury activates both proliferative and antiproliferative pathways, the consequences of which are not fully elucidated. If an initial proliferation of the renal epithelium is necessary for the successful repair, the persistence of proliferation markers is associated with the occurrence of chronic kidney disease. We hypothesized that proliferation in stress conditions impacts cell viability and renal outcomes. We found that proliferation is associated with cell death after various stresses in kidney cells. In vitro, the ATP/ADP ratio oscillates reproducibly throughout the cell cycle, and cell proliferation is associated with a decreased intracellular ATP/ADP ratio. In vivo, transcriptomic data from transplanted kidneys revealed that proliferation was strongly associated with a decrease in the expression of the mitochondria-encoded genes of the oxidative phosphorylation pathway, but not of the nucleus-encoded ones. These observations suggest that mitochondrial function is a limiting factor for energy production in proliferative kidney cells after injury. The association of increased proliferation and decreased mitochondrial function was indeed associated with poor renal outcomes. In summary, proliferation is an energy-demanding process impairing the cellular ability to cope with an injury, highlighting proliferative repair and metabolic recovery as indispensable and interdependent features for successful kidney repair. [ABSTRACT FROM AUTHOR]

Background: Pulmonary alveolar proteinosis (PAP) is a rare syndrome caused by several distinct diseases leading to progressive dyspnoea, hypoxaemia, risk of respiratory failure and early death due to accumulation of proteinaceous material in the lungs. Diagnostic strategies may include computed tomography (CT) of the lungs, bronchoalveolar lavage (BAL), evaluation of antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), genetic testing and, eventually, lung biopsy. The management options are focused on removing the proteinaceous material by whole lung lavage (WLL), augmentation therapy with GM-CSF, rituximab, plasmapheresis and lung transplantation. The presented diagnostic and management guidelines aim to provide guidance to physicians managing patients with PAP., Methods: A European Respiratory Society Task Force composed of clinicians, methodologists and patients with experience in PAP developed recommendations in accordance with the ERS Handbook for Clinical Practice Guidelines and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. This included a systematic review of the literature and application of the GRADE approach to assess the certainty of evidence and strength of recommendations. The Task Force formulated five PICO (Patients, Intervention, Comparison, Outcomes) questions and two narrative questions to develop specific evidence-based recommendations., Results: The Task Force developed recommendations for the five PICO questions. These included management of PAP with WLL, GM-CSF augmentation therapy, rituximab, plasmapheresis and lung transplantation. Also, the Task Force made recommendations regarding the use of GM-CSF antibody testing, diagnostic BAL and biopsy based on the narrative questions. In addition to the recommendations, the Task Force provided information on the hierarchy of diagnostic interventions and therapy., Conclusions: The diagnosis of PAP is based on CT and BAL cytology or lung histology, whereas the diagnosis of specific PAP-causing diseases requires GM-CSF antibody testing or genetic analysis. There are several therapies including WLL and augmentation therapy with GM-CSF available to treat PAP, but supporting evidence is still limited., Competing Interests: Conflict of interest: C. McCarthy, F. Bonella, B.C. Trapnell and M. Griese report membership of a scientific advisory board of Savara Inc. B.C. Trapnell reports grants from the NHLBI (HL085453) and Savara, consultancy fees from Savara, and support for attending meetings from Savara. T. Wang reports grants from Savara, consultancy fees from Partner Therapeutics and Savara, payment or honoraria for lectures, presentations, manuscript writing or educational events from Partner Therapeutics and Savara, support for attending meetings from the PAP Foundation, participation on a data safety monitoring board or advisory board with Partner Therapeutics and Savara Inc., and a leadership role with the PAP Foundation (Clinical Director and Vice President). C. McCarthy reports grants from Health Research Board, Ireland, Enterprise Ireland and The LAM Foundation, consultancy fees from Theravance Inc., Savara Inc. and AI Therapeutics, support for attending meetings from Boehringer Ingelheim, and participation on a data safety monitoring board or advisory board with Savara Inc. F. Bonella reports consultancy fees from Boehringer Ingelheim, Sanofi, BMS and Savara Inc., payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim and Sanofi, support for attending meetings from Boehringer Ingelheim, AstraZeneca, Atyr and Savara Pharma, and participation on a data safety monitoring board or advisory board with Boehringer Ingelheim, Sanofi and BMS. M. Fally reports leadership roles with the European Respiratory Society (Member of the Clinical Practice Guidelines Methodology Network and Secretary of Assembly 10, Group 1) and Danish Medical Journal (Associate Editor). A. Hadchouel reports patent issued (PCT/EP2022/064179). S. Jouneau reports the following financial (or non-financial) interests: PI for IMPALA and IMPALA-2 studies (Savara Inc.). R. Borie reports honoraria from Boehringer Ingelheim, Sanofi and Ferrer, support for attending meetings from Boehringer Ingelheim, and participation on a data safety monitoring board or advisory board with Savara. I. Campo reports consultancy fees from Partner's Therapeutics, and participation on a data safety monitoring board or advisory board with Savara. E. Manali reports grants from Savara, consulting fees from Boehringer Ingelheim, CLS Behring and Hoffman-La Roche, payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim, CLS Behring and Hoffman-La Roche, support for attending meetings from Boehringer Ingelheim, CLS Behring, Hoffman-La Roche and Elpen, and a leadership role with the European Respiratory Society (Chair in ERS Task Force for Transition of chILD). H. Prosch reports grants from Boehringer Ingelheim, AstraZeneca, Siemens Healthineers, the Christian Doppler Research Association and EU Commission (EU4Health, Horizon Europe Health), consultancy fees from Boehringer Ingelheim and Sanofi, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, BMS, Boehringer Ingelheim, Bracco, Daiichi Sankyo, Janssen, MSD, Novartis, Roche, Sanofi, Siemens Healthineers and Takeda, support for attending meetings from Boehringer Ingelheim, participation on a data safety monitoring board or advisory board with Boehringer Ingelheim, and a leadership role with the European Society of Thoracic Imaging (Vice President). M. Veltkamp reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim and Chiesi, and participation on a data safety monitoring board or advisory board with Boehringer Ingelheim and Xentria. E. Bendstrup reports honoraria from Boehringer Ingelheim, AstraZeneca and Daichii Sankyo, support for attending meetings from Boehringer Ingelheim, and participation on a data safety monitoring board or advisory board with Boehringer Ingelheim and Simbec-Orion. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

The main monogenic causes of pulmonary fibrosis in adults are mutations in telomere-related genes. These mutations may be associated with extrapulmonary signs (hepatic, haematological and dermatological) and typically present radiologically as usual interstitial pneumonia or unclassifiable fibrosis. In children, the monogenic causes of pulmonary fibrosis are dominated by mutations in surfactant-related genes. These mutations are not associated with extrapulmonary signs and often manifest radiologically as unclassifiable fibrosis with cysts that can lead to chest wall deformities in adults. This review discusses these mutations, along with most of the monogenic causes of interstitial lung disease, including interferon-related genes, mutations in genes causing cystic lung disease, Hermansky-Pudlak syndrome, pulmonary alveolar proteinosis, lysinuric protein intolerance and lysosomal storage disorders, and their pulmonary and extrapulmonary manifestations., Competing Interests: Conflict of interest: R. Borie reports consultancy fees from Boerhinger Ingelheim, Ferrer and Sanofi, payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim, and support for attending meetings from Boehringer Ingelheim. L. Berteloot and C. Kannengiesser have nothing to disclose. M. Griese reports grants from Deutsche Forschungsgemeinschaft, and participation on a data safety monitoring board or advisory board with Boehringer Ingelheim. A. Cazes reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim. B. Crestani reports grants from Boehringer Ingelheim, consultancy fees from BMS, Boehringer Ingelheim, Chiesi, CSL Behring, GSK and Sanofi, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, BMS, Boehringer Ingelheim, GSK, Novartis, Roche and Sanofi, support for attending meetings from AstraZeneca, BMS, Boehringer Ingelheim, Roche and Sanofi, participation on a data safety monitoring board or advisory board with BMS, Boehringer Ingelheim, Horizon and Sanofi, and a leadership role with Fondation du Souffle (President of the board of trustees). A. Hadchouel has nothing to disclose. M.P. Debray reports consultancy fees from Boehringer Ingelheim, payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim, Sanofi and Bracco, and support for attending meetings from Boehringer Ingelheim., (Copyright ©The authors 2024.)

Genetic autoinflammatory diseases are now a recognized and rapidly expanding group. The lung involvement historically associated with autoinflammatory diseases is inflammatory seritis, primarily seen in familial Mediterranean fever and other interleukin-1 mediated diseases. Over the last ten years, pulmonary involvement has been the core presentation of two autoinflammatory diseases associated with constitutive type I interferon activation, i.e. SAVI and COPA syndrome. Most patients with these diseases usually develop early progression to pulmonary fibrosis, which is responsible for high rates of morbidity and mortality. Other rare autoinflammatory diseases are associated with alveolar proteinosis, particularly when related to MARS mutations. Additionally, in adults, VEXAS is frequently associated with pulmonary involvement, albeit without prognosis effect. A molecular approach to autoinflammatory diseases enables not only the definition of biomarkers for diagnosis, but also the identification of targeted treatments. Examples include JAK inhibitors in SAVI and COPA syndrome, even though this therapy does not prevent progression to pulmonary fibrosis. Another illustrative example is the efficacy of methionine supplementation in alveolar proteinosis linked to MARS mutations. Overall, in autoinflammatory diseases the lung is now emerging as a possible affected organ. Continuing discovery of new autoinflammatory diseases is likely to uncover further pathologies involving the lung. Such advances are expected to lead to the development of novel therapeutic perspectives., (Copyright © 2023. Published by Elsevier Masson SAS.)