TRPV1 is a Ca2+-permeable channel mostly studied as a pain receptor in sensory neurons. However, its role in other cell types is poorly understood. Here, we demonstrate that TRPV1 is functionally expressed in CD4+ T cells where it acts as a non-store-operated Ca2+ channel and contributes to T cell receptor (TCR)-induced Ca2+ influx, TCR signaling and T cell activation. In models of T cell-mediated colitis, TRPV1 promotes colitogenic T cell responses and intestinal inflammation. Furthermore, genetic and pharmacological inhibition of TRPV1 in human CD4+ T cells recapitulates the phenotype of murine Trpv1−/− CD4+ T cells. These findings suggest that TRPV1 inhibition could represent a new therapeutic strategy to restrain proinflammatory T cell responses.

No abstract

Macrophage activation by the proinflammatory cytokine interferon-␥ (IFN-␥[Keywords: Mitochondria; macrophages; Listeria monocytogenes; oxidative metabolism; reactive oxygen species] Supplemental material is available at http://www.genesdev.org.

A hallmark of rheumatoid arthritis is the formation of an aggressive, tumor-like structure called pannus that erodes the joint. A major cellular component of the pannus is the fibroblast-like synoviocyte (FLS), whose morphology strikingly resembles that of a transformed cell, but underlying mechanisms of this ''transformation'' are not known. Here, using animal models of rheumatoid arthritis, we show that arthritic FLS contain a substantial (>30%) fraction of bone marrow-derived precursors that can differentiate in vitro into various mesenchymal cell types, but inflammation prevents the multilineage differentiation. We show that the transcription factor NF-B plays the key role in the repression of osteogenic and adipogenic differentiation of arthritic FLS. Furthermore, we show that specific activation of NF-B profoundly enhances proliferation, motility, and matrix-degrading activity of FLS. We thus propose that arthritic FLS are mesenchymal stem cells whose differentiation is arrested at early stages of differentiation by activation of NF-B.fibroblast-like synoviocytes ͉ mesenchymal stem cell ͉ rheumatoid arthritis

Tumor hypoxia, the "Achilles heel" of current cancer therapies,i si ndispensable to drug resistance and poor therapeutic outcomes especially for radiotherapy. Here we propose an in situ catalytic oxygenation strategy in tumor using porphyrinic metal-organic framework (MOF)-gold nanoparticles (AuNPs) nanohybrid as atherapeutic platform to achieve O 2 -evolving chemoradiotherapy. The AuNPs decorated on the surface of MOF effectively stabilize the nanocomposite and serve as radiosensitizers,w hereas the MOF scaffold acts as acontainer to encapsulate chemotherapeutic drug doxorubicin. In vitro and in vivo studies verify that the catalase-like nanohybrid significantly enhances the radiotherapye ffect, alleviating tumor hypoxia and achieving synergistic anticancer efficacy.T his hybrid nanomaterial remarkably suppresses the tumor growth with minimized systemic toxicity,o pening new horizons for the next generation of theranostic nanomedicines.