Formation of Human Thymus Organoids in Three-Dimensional Fibrin Hydrogels

International audienceGeneration of a functional and self-tolerant T cell repertoire is a complex process dependent on the thymic microenvironment and, primarily, on the properties of its extracellular matrix (ECM). Thymic epithelial cells (TECs) are crucial in thymopoiesis, nurturing and selecting developing T cells by filtering self-reactive clones. TECs have been empirically demonstrated to be particularly sensitive to physical and chemical clues supplied by the ECM and classical monolayer cell culture leads to a quick loss of functionality until their death. Because of this delicate maintenance combined with relative rarity, and despite the high stakes in modeling thymus biology in vitro, models able to faithfully mimic the TEC niche at scale and over time are still lacking. Here, we describe the formation of a multicellular human thymic organoid model, in which the TEC compartment is derived from human induced pluripotent stem cells (iPSC) and reaggregated with primary early thymocyte progenitors in a three-dimensional (3D) fibrin-based hydrogel. This model answers current needs for a scalable culture system that reproduces the thymic microenvironment ex vivo and demonstrates functionality, i.e., the ability to produce T cells and to support thymus organoid growth over several weeks. Thus, we propose a practical in vitro model of thymus functionality through iPSC-derived organoids that would benefit research on TEC biology and T cell generation ex vivo

Progressive neurologic disorder: Initial manifestation of hemophagocytic lymphohistiocytosis

Legacy description not available</p

Progressive neurologic disorder: Initial manifestation of hemophagocytic lymphohistiocytosis

Legacy description not available</p

Mycoplasma pneumoniae infection in adult inpatients during the 2023–24 outbreak in France (MYCADO): a national, retrospective, observational study

International audienceBackground. An epidemic of Mycoplasma pneumoniae infection has been observed in France since the fall of 2023. We aimed to: i) describe the characteristics of adults hospitalized for M. pneumoniae infection and ii) identify factors associated with severe outcomes of infection (i.e., intensive care unit [ICU)] admission or in-hospital death).Methods. MYCADO is a retrospective observational study including adults hospitalized for ≥24 hours in 76 French hospitals for a M. pneumoniae infection between 1 September 2023 and 29 February 2024. Clinical, laboratory and imaging data were collected from medical records.We identified factors associated with severe outcomes of infection, defined as need for ICU or in-hospital death, using multivariable logistic regression.Findings. Overall, 1309 patients with M. pneumoniae infection were included: 718 (54.9%) males; median age 43 years (IQR 31-63); 288 (22.0%) with chronic respiratory failure; 423 (32.3%) with cardiovascular comorbidities; 95 (7.3%) with immunosuppression. The most common symptoms were: cough (n=1098, 83.9%), fever (n=1023, 78.2%), dyspnoea (n=948, 72.4%), fatigue (n=550, 42.0%), headache (n=211, 16.1%), arthromyalgia (n=253, 19.3%), vomiting (n=132, 10.1%); 156 (11.9%) patients had extra-respiratory manifestations, including 36 (2.8%) erythema multiforme, 19 (1.5%) meningoencephalitis, 44 (3.4%) autoimmune haemolytic anaemia and 17 (1.3%) myocarditis. The median hospital stay duration was 8 days (IQR 6-11); 415 (31.7%) patients were admitted to ICU and 28 (2.1%) died at hospital. Men, patients with hypertension, obesity, respiratory or liver chronic failure, extra-respiratory manifestations, bilateral lung damage or consolidation on computed tomography scan, elevated inflammatory syndrome, lymphopenia, and those who did not receive any active antibiotic against M. pneumoniae prior to admission, were more likely to present with severe outcomes of infection.Interpretation. This national, observational study highlights unexpected, atypical radiologic presentations, a high proportion of transfers to ICU, and an association between severity and delayed administration of effective antibiotics