Institut Cochin

Antibody-mediated immune surveillance as an organizing axis of gut microbiota structure

Abstract Background The symbiotic interplay between the immune system and the endogenous microbiome is essential for maintaining homeostasis. However, most microbiome research focuses primarily on associations between disease and microbial composition, often overlooking host–micr...

A DNA methylation–based risk score improves prognostic stratification in myelodysplastic neoplasms

Myelodysplastic neoplasms (MDS) are clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and variable risk of progression to acute myeloid leukemia (AML). Although mutational data are already implemented into the most recent MDS risk models, (i.e...

Transarterial embolization in musculoskeletal care: an indication-stratified narrative review

Abstract Background Transarterial embolization (TAE) is increasingly used across a broad spectrum of musculoskeletal conditions, ranging from established hemostatic and tumor-related indications to emerging pain-directed procedures for degenerative joint disease and chronic infla...

BRET-Based Mitochondrial Subcompartment Localization Biosensors Reveal the Impact of Pesticides and Food Additives on Mitochondrial Protein Localization

Abstract The last decade has witnessed a marked increase in interest in mitochondria, whose dysfunction leads to the development of multiple diseases. Mitochondria are unique as they are highly compartmentalized organelles that are composed of two closely apposed membranes. Here,...

Distinct migratory dendritic cell subsets cooperate to prime tissue-resident memory-like CD8⁺ T cells in mouse tumors

Tumor-infiltrating tissue-resident memory (TRM)-like CD8+ T cells correlate with positive prognosis and better responses to cancer immunotherapy, yet the mechanisms underlying their specification remain ill-understood. Here, we use the KP (KrasG12D, p53-/-) mouse model of lung ad...

Parallel regulation of tissue morphogenesis and cell fate specification by RAR:RXR signalling during pancreas formation

During embryogenesis, morphologically diverse epithelial organs bud from different regions of the embryonic gut. The unique features of each nascent organ result from distinct cell fate specification and morphogenetic events elicited by organ-inducing cues. Retinoic acid is a pow...

The GPCRVP score reliably predicts the impact of GLP1R human variants on receptor function

Abstract Aims/hypothesis The glucagon-like peptide-1 receptor (GLP1R) is a key regulator of glucose homeostasis and body weight, and a major therapeutic target for type 2 diabetes and obesity. Individual disease risk and response to treatments may vary widely depending on the pre...

International consensus guidance for general population screening for islet autoantibodies to diagnose early-stage type 1 diabetes: a nominal group technique process

Type 1 diabetes is an autoimmune disease that targets and destroys insulin-producing beta cells in the pancreatic islets. The incidence of type 1 diabetes is rising globally. At the clinical diagnosis of type 1 diabetes, between 20% and 67% of children and adolescents present wit...

Human-inherited RORγT deficiency encompasses genetic heterogeneity, T cell deficiency, and clinical homogeneity

Abstract We previously reported inherited RORγT deficiency in seven patients from three ancestries (Chilean, Palestinian, Saudi Arabian) with mycobacterial disease and chronic mucocutaneous candidiasis (CMC). We report here five additional patients from different ancestries (Afgh...

Calpain inhibition prevents high-glucose-induced autophagy blockade and mitochondrial fragmentation in endothelial cells and preserves vascular functions in diabetic mice

Endothelial dysfunction is a major contributor to diabetic vascular complications, yet the mechanisms linking hyperglycemia to impaired endothelial homeostasis remain insufficiently defined. This study identifies calpains as key regulators of endothelial autophagy and mitophagy u...

The identification of a PRKACA duplication at 19p13.12 in a female with PPNAD and thyroid carcinoma after a 20-year diagnostic journey

Abstract Rare pathogenic variants affecting components of the evolutionary conserved cAMP/protein kinase A (PKA) signalling pathway are implicated in a spectrum of adrenocortical disorders. Germline inactivating PRKAR1A variants leading to constitutive PKA activation, underlie pr...

An N-terminal CDC42 T43I variant reveals the mechanism of pyrin inflammasome activation

Heterozygous carboxyl-terminal variants in the RHO guanosine triphosphatase (GTPase) CDC42 are known to cause severe autoinflammatory syndromes. Here, we identified a heterozygous amino-terminal p.T43I (Thr 43 →Ile) CDC42 variant in patients with autoinflammation and uncovered a...

Visible mould and blood inflammatory phenotypes of asthma in adults: the CONSTANCES cohort

Studying the associations between indoor mould contamination and blood inflammatory phenotypes may provide further insight into the mechanisms by which this environmental factor affects asthma. Among 1870 adults with current asthma from a population-based cohort, 29.6% reported v...