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.
Researching Metaphor in the Ancient Near East. Edited by Marta Pallavidini and Ludovico Portuese. Philippika, vol. 141. Wiesbaden: Harrassowitz Verlag, 2020. Pp. xxi + 270, illus. €49 (paper).
In Hittite religious texts, many references to human consumption or, on the contrary, to prohibiting human consumption of sacrificial food are made, but they have not yet been studied as such. This ...paper will endeavor to fill this gap by gathering the data for the first time. It will also examine them in context in order to better understand the underlying mechanism of human consumption of consecrated food in Hittite Anatolia.
Abstract
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.
Mythopoeïa ou l’art de forger les “mythes” dans l’“aire culturelle” syro-mésopotamienne, méditerranéenne et indo-européenne. By Jérôme Pace. State Archives of Assyria Studies, vol. 27. ...Helsinki: The Neo-Assyrian Text Corpus ProJect, 2018. Pp. xxvii + 343. $89.50 (paper). Distributed by Penn State University Press, State College, PA
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