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"Mouton, Alice"
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Extracellular traps released by antimicrobial TH17 cells contribute to host defense
TH17 cell subpopulations have been defined that contribute to inflammation and homeostasis, yet the characteristics of TH17 cells that contribute to host defense against infection are not clear. To elucidate the antimicrobial machinery of the TH17 subset, we studied the response to Cutibacterium acnes, a skin commensal that is resistant to IL-26, the only known TH17-secreted protein with direct antimicrobial activity. We generated C. acnes-specific antimicrobial TH17 clones (AMTH17) with varying antimicrobial activity against C. acnes, which we correlated by RNA sequencing to the expression of transcripts encoding proteins that contribute to antimicrobial activity. Additionally, we validated that AMTH17-mediated killing of C. acnes and bacterial pathogens was dependent on the secretion of granulysin, granzyme B, perforin, and histone H2B. We found that AMTH17 cells can release fibrous structures composed of DNA decorated with histone H2B that entangle C. acnes that we call T cell extracellular traps (TETs). Within acne lesions, H2B and IL-17 colocalized in CD4+ T cells, in proximity to TETs in the extracellular space composed of DNA decorated with H2B. This study identifies a functionally distinct subpopulation of TH17 cells with an ability to form TETs containing secreted antimicrobial proteins that capture and kill bacteria.
Journal Article
NOTUM promotes thermogenic capacity and protects against diet-induced obesity in male mice
We recently showed that NOTUM, a liver-secreted Wnt inhibitor, can acutely promote browning of white adipose. We now report studies of chronic overexpression of NOTUM in liver indicating that it protects against diet-induced obesity and improves glucose homeostasis in mice. Adeno-associated virus (AAV) vectors were used to overexpress GFP or mouse
Notum
in the livers of male C57BL/6J mice and the mice were fed an obesifying diet. After 14 weeks of high fat, high sucrose diet feeding, the AAV-Notum mice exhibited decreased obesity and improved glucose tolerance compared to the AAV-GFP mice. Gene expression and immunoblotting analysis of the inguinal fat and brown fat revealed increased expression of beige/brown adipocyte markers in the AAV-Notum group, suggesting enhanced thermogenic capacity by NOTUM. A β3 adrenergic receptor agonist-stimulated lipolysis test suggested increased lipolysis capacity by NOTUM. The levels of collagen and C–C motif chemokine ligand 2 (CCL2) in the epididymal white adipose tissue of the AAV-Notum mice were significantly reduced, suggesting decreased fibrosis and inflammation, respectively. RNA sequencing analysis of inguinal white adipose of 4-week chow diet-fed mice revealed a highly significant enrichment of extracellular matrix (ECM) functional cluster among the down-regulated genes in the AAV-Notum group, suggesting a potential mechanism contributing to improved glucose homeostasis. Our in vitro studies demonstrated that recombinant human NOTUM protein blocked the inhibitory effects of WNT3A on brown adipocyte differentiation. Furthermore, NOTUM attenuated WNT3A’s effects on upregulation of TGF-β signaling and its downstream targets. Overall, our data suggest that NOTUM modulates adipose tissue function by promoting thermogenic capacity and inhibiting fibrosis through inhibition of Wnt signaling.
Journal Article
Genomic insights into the population structure and adaptive variation of Mullus barbatus in the Mediterranean Sea
Background
Red mullet (
Mullus barbatus
) is a key species in Mediterranean fisheries, yet its stock structure and population dynamics remain poorly understood due to a lack of comprehensive genomic resources. This study provides the first high-quality reference genome for
M. barbatus
and a comprehensive set of SNP markers to investigate its population structure and adaptive potential across the Mediterranean.
Results
Using the newly generated chromosome-level reference genome, we re-analyzed a Mediterranean-wide reduced-representation genomic dataset. Our analysis reveals a panmictic population structure with strong genetic connectivity across the species’ range, likely driven by extensive larval dispersal and multigenerational gene flow. Despite minimal genome-wide differentiation, outlier analysis identified candidate loci under directional selection, linked to key biological processes such as ontogeny and environmental adaptation.
Conclusions
This study presents the first genomic resource for
M. barbatus
, providing valuable insights into its genetic structure and adaptive mechanisms. While the identification of loci under selection offers promising leads, these findings are preliminary due to the limited genomic coverage of the dataset. Nonetheless, they pave the way for future genomic studies to explore how
M. barbatus
adapts to environmental and anthropogenic pressures. These results hold significant implications for the sustainable management of Mediterranean fisheries, especially in the context of climate change and conservation.
Journal Article
Genetic structure of fragmented southern populations of African Cape buffalo (Syncerus caffer caffer)
Background
African wildlife experienced a reduction in population size and geographical distribution over the last millennium, particularly since the 19
th
century as a result of human demographic expansion, wildlife overexploitation, habitat degradation and cattle-borne diseases. In many areas, ungulate populations are now largely confined within a network of loosely connected protected areas. These metapopulations face gene flow restriction and run the risk of genetic diversity erosion. In this context, we assessed the “genetic health” of free ranging southern African Cape buffalo populations (
S.c. caffer
) and investigated the origins of their current genetic structure. The analyses were based on 264 samples from 6 southern African countries that were genotyped for 14 autosomal and 3 Y-chromosomal microsatellites.
Results
The analyses differentiated three significant genetic clusters, hereafter referred to as Northern (N), Central (C) and Southern (S) clusters. The results suggest that splitting of the N and C clusters occurred around 6000 to 8400 years ago. Both N and C clusters displayed high genetic diversity (mean allelic richness (
A
r
) of 7.217, average genetic diversity over loci of 0.594, mean private alleles (
P
a
) of 11), low differentiation, and an absence of an inbreeding depression signal (mean
F
IS
= 0.037). The third (S) cluster, a tiny population enclosed within a small isolated protected area, likely originated from a more recent isolation and experienced genetic drift (
F
IS
= 0.062, mean
A
r
= 6.160,
P
a
= 2). This study also highlighted the impact of translocations between clusters on the genetic structure of several African buffalo populations. Lower differentiation estimates were observed between C and N sampling localities that experienced translocation over the last century.
Conclusions
We showed that the current genetic structure of southern African Cape buffalo populations results from both ancient and recent processes. The splitting time of N and C clusters suggests that the current pattern results from human-induced factors and/or from the aridification process that occurred during the Holocene period. The more recent S cluster genetic drift probably results of processes that occurred over the last centuries (habitat fragmentation, diseases). Management practices of African buffalo populations should consider the micro-evolutionary changes highlighted in the present study.
Journal Article
