Biology subjects

Thibault, J.

Publications and source records attributed to Thibault, J..

4 recordsLinked to original sources

bioRxiv2024

CD271 restrains the B1b cell antibody response in a T cell dependent manner

Co-signaling molecules modulate T cell function and are essential to control the duration and amplitude of immune responses. These molecules belong to the immunoglobulin and tumor necrosis factor receptor (TNFR) superfamilies and have been extensively studied; however, the immunomodulatory role of several family members remains unknown. We show that CD271 (also known as p75 or NGFR), a TNFR superfamily member, is highly expressed on peritoneal B1 B cells, but not on conventional (B2) B cells at steady state. CD271 expression by B cells specifically restrains the response to T cell-independent type 2 antigens (TI-2). B1 cell-expressed CD271 maintains peritoneal CD4+ T cell quiescence, and augmented antibody responses to TI-2 antigens in CD271-deficient mice are dependent on CD4+ T cells. This increase in antibody production correlates with improved bacterial neutralization in vitro and survival after bacterial challenge in vivo. Further, our results suggest that CD271 can directly inhibit mouse and human T cell activity to the same extent as PD-L1, a known, negative regulator of T cell function. These results establish CD271 as a co-inhibitory molecule that could be targeted to improve the efficacy of vaccines against pathogenic encapsulated bacteria and to broadly modulate the T cell response in therapeutic contexts. eTOC summaryLebel et al. identify an unexpected role for CD271, a neurotrophin receptor, in directly inhibiting T cell function. B1 cell-expressed CD271 maintains CD4+ T cell quiescence; in the absence of CD271, T cells bolster antibody production to T-independent antigens, enhancing the response to encapsulated bacteria.

immunology↗

bioRxiv2022

ROCK2 Knockout Improves Proliferation Rate in a Cellular Model of Down Syndrome

In a cellular model of Down Syndrome, hTERT immortalized RPE-1 (human retinal pigment epithelial-1) cells carrying an extra copy of chromosome 21 exhibit reduced fitness, in part, as an increase in doubling time (or a reduction in cell proliferation rate) in culture. ROCK2 (Rho associated coiled-coil containing kinase 2) was identified in a whole genome CRISPR knockout (KO) screen designed to identify genes and pathways that could be therapeutically targeted to improve cell proliferation (Replogle JM, et al. manuscript in preparation). ROCK2 KO cell lines of both RPE-1 euploid and trisomy 21 aneuploid cells were created using CRISPR. Trisomy 21 ROCK2 KO cell lines showed a modest increase in cell proliferation rate compared to the parental aneuploid cells, similar to the relative effect that ROCK2 knockout had in the whole genome CRISPR screen. Euploid ROCK2 KO cell lines showed no difference in growth rate vs their ROCK2 expressing counterparts. Changes in doubling time in response to two pharmaceutical ROCK inhibitors, Fasudil and Y27632, also showed the same modest increase in cell proliferation rate in the trisomy 21 cells. The actin cytoskeleton, a target of ROCK2 regulation, exhibited long stress fibers that aligned across multiple contiguous cells in confluent trisomy 21 ROCK2 KO cells compared to the disorganized stress fibers of the parental trisomy 21 cells with normal ROCK2 expression.

cell biology↗

bioRxiv2022

Kiawah and Seabrook islands are a critical site for the rufa red knot (Calidris canutus rufa)

The rufa Red Knot (Calidris canutus rufa) is a migratory shorebird that performs one of the longest known migrations of any bird species -- from their breeding grounds in the Canadian Arctic to their nonbreeding grounds as far south as Tierra del Fuego -- and has experienced a population decline of over 85% in recent decades. During migration, knots rest and refuel at stopover sites along the Atlantic Coast, including Kiawah and Seabrook islands in South Carolina. Here, we document the importance of Kiawah and Seabrook islands for knots by providing population and stopover estimates during their spring migration. We conducted on-the-ground surveys between 19 February - 20 May 2021 to record the occurrence of individually marked knots. In addition, we quantified the ratio of marked to unmarked knots and deployed geolocators on knots captured in the area. Using a superpopulation model, we estimated a minimum passage population of 17,247 knots (~41% of the total rufa knot population) and an average stopover duration of 47 days. Our geolocator results also showed that knots using Kiawah and Seabrook islands can bypass Delaware Bay and fly directly to the Canadian Arctic. Finally, our geolocators, combined with resighting data from across the Atlantic Flyway, indicate that a large network of more than 70 coastal sites mostly concentrated along the coasts of Florida, Georgia, South Carolina, and North Carolina provide stopover and overwintering habitat for the knots we observed on Kiawah and Seabrook islands. These findings corroborate that Kiawah and Seabrook islands should be recognized as critical sites in the knot network and, therefore, a conservation priority. As a result, the threats facing the sites -- such as prey management issues, anthropogenic disturbance, and sea level rise -- require immediate attention.

ecology↗

bioRxiv2017

Scaling accurate genetic variant discovery to tens of thousands of samples

Comprehensive disease gene discovery in both common and rare diseases will require the efficient and accurate detection of all classes of genetic variation across tens to hundreds of thousands of human samples. We describe here a novel assembly-based approach to variant calling, the GATK HaplotypeCaller (HC) and Reference Confidence Model (RCM), that determines genotype likelihoods independently per-sample but performs joint calling across all samples within a project simultaneously. We show by calling over 90,000 samples from the Exome Aggregation Consortium (ExAC) that, in contrast to other algorithms, the HC-RCM scales efficiently to very large sample sizes without loss in accuracy; and that the accuracy of indel variant calling is superior in comparison to other algorithms. More importantly, the HC-RCM produces a fully squared-off matrix of genotypes across all samples at every genomic position being investigated. The HC-RCM is a novel, scalable, assembly-based algorithm with abundant applications for population genetics and clinical studies.

genomics↗