Biology subjects

Trottein, F.

Publications and source records attributed to Trottein, F..

2 recordsLinked to original sources

bioRxiv2020

The hypothalamus as a hub for putative SARS-CoV-2 brain infection

Most patients with COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), display neurological symptoms, and respiratory failure in certain cases could be of extra-pulmonary origin. Hypothalamic neural circuits play key roles in sex differences, diabetes, hypertension, obesity and aging, all risk factors for severe COVID-19, besides being connected to olfactory/gustative and brainstem cardiorespiratory centers. Here, human brain gene-expression analyses and immunohistochemistry reveal that the hypothalamus and associated regions express angiotensin-converting enzyme 2 and transmembrane proteinase, serine 2, which mediate SARS-CoV-2 cellular entry, in correlation with genes or pathways involved in physiological functions or viral pathogenesis. A post-mortem patient brain shows viral invasion and replication in both the olfactory bulb and the hypothalamus, while animal studies indicate that sex hormones and metabolic diseases influence this susceptibility.

neuroscience↗

bioRxiv2020

High dimensional single-cell analysis reveals iNKT cell developmental trajectories and effector fate decision

CD1d-restricted invariant Natural Killer T (iNKT) cells represent a unique class of T lymphocytes endowed with potent regulatory and effector immune functions. Although these functions are acquired during thymic ontogeny, the sequence of events that give rise to discrete effector subsets remains unclear. Using an unbiased single-cell transcriptomic analysis combined with functional assays, we revealed an unappreciated diversity among thymic iNKT cells, especially among iNKT1 cells. Mathematical modelling and biological methods unravelled a developmental map whereby iNKT2 cells constitute a transient branching point towards the generation of iNKT1 and iNKT17 cells, which reconciles the two previously proposed models. In addition, we identified the transcription co-factor Four-and-a-half LIM domains protein 2 (FHL2) as a critical cell-intrinsic regulator of iNKT1 specification. Thus, these data illustrate the changing transcriptional network that guides iNKT cell effector fate.

immunology↗