Author’s Place, Digital Space: Mapping Tennessee Williams, 1938-1948

From 1938-­1948, twentieth-­century American author Tennessee Williams traveled the country with his portable typewriter and a battered suitcase. He wrote every day, and his writings reflect the places and people he encountered. Williams’s journey from obscurity to fame as a writer during this decade parallels the nation’s path from depression to postwar prosperity. The events of this time period remain scattered across Williams’s scholarship; however, our collaborative, interdisciplinary project takes advantage of new methods of investigation and dissemination to create a multimedia map that traces the writer’s movements. We use Google Earth to create placemarks that highlight Williams’s professional and personal connections, production histories, and social and political contexts. This highly visual multi­dimensional map acts as a resource for academic and general audiences by providing access to secondary sources and to excerpts from Williams’s plays, stories, letters, and journal entries. Users will gain a greater understanding of Williams and his world by engaging with this interactive mapping project

Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth

International audienceChemotherapeutic agents are widely used for cancer treatment. In addition to their direct cytotoxic effects, these agents harness the host's immune system, which contributes to their antitumor activity. Here we show that two clinically used chemotherapeutic agents, gemcitabine (Gem) and 5-fluorouracil (5FU), activate the NOD-like receptor family, pyrin domain containing-3 protein (Nlrp3)-dependent caspase-1 activation complex (termed the inflammasome) in myeloid-derived suppressor cells (MDSCs), leading to production of interleukin-1β (IL-1β), which curtails anticancer immunity. Chemotherapy-triggered IL-1β secretion relied on lysosomal permeabilization and the release of cathepsin B, which bound to Nlrp3 and drove caspase-1 activation. MDSC-derived IL-1β induced secretion of IL-17 by CD4+ T cells, which blunted the anticancer efficacy of the chemotherapy. Accordingly, Gem and 5FU exerted higher antitumor effects when tumors were established in Nlrp3−/− or Casp1−/− mice or wild-type mice treated with interleukin-1 receptor antagonist (IL-1Ra). Altogether, these results identify how activation of the Nlrp3 inflammasome in MDSCs by 5FU and Gem limits the antitumor efficacy of these chemotherapeutic agents

The interleukin-1 family: back to the future

Item does not contain fulltextInterleukin-1 (IL-1) is a central mediator of innate immunity and inflammation. The IL-1 family includes seven ligands with agonist activity (IL-1alpha and IL-1beta, IL-18, IL-33, IL-36alpha, IL-36beta, IL-36gamma), three receptor antagonists (IL-1Ra, IL-36Ra, IL-38), and an anti-inflammatory cytokine (IL-37). Members of the IL-1 Receptor (IL-1R) family include six receptor chains forming four signaling receptor complexes, two decoy receptors (IL-1R2, IL-18BP), and two negative regulators (TIR8 or SIGIRR, IL-1RAcPb). A tight regulation via receptor antagonists, decoy receptors, and signaling inhibitors ensures a balance between amplification of innate immunity and uncontrolled inflammation. All cells of the innate immune system express and/or are affected by IL-1 family members. Moreover, IL-1 family members play a key role in the differentiation and function of polarized innate and adaptive lymphoid cells. Here we will review the key properties of IL-1 family members, with emphasis on pathways of negative regulation and orchestration of innate and adaptive immunity