Although recent progress has aided our understanding of the processes that prevent immune tolerance breakdown, this Focus issue illustrates how much remains unknown about susceptibility to and pathogenesis of autoimmune diseases.
Volume 11 Issue 1, January 2010
News & Views
The present views of how CD4+ T cells respond to antigen are based largely on artificial systems. A highly sensitive approach that allows normal T cell responses to be monitored in physiological conditions overturns some existing ideas about the differentiation of CD4+ T cells.
The mammalian intestine contains a large number of commensal bacterial strains. New work suggests that antimicrobial peptides used for defense against pathogenic bacteria are also used to adjust the balance among bacterial populations and to control intestinal homeostasis.
Recent advances in microscopy have enabled imaging of cell surface receptors at ever higher resolutions. A report using the latest technology now provides evidence that the T cell antigen receptor and the adaptor Lat are confined to small islands, which cluster together after triggering of the T cell antigen receptor.
Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry
Autophagy facilitates host defense against invading bacteria. Philpott and colleagues show that Nod1 and Nod2 link pathogen sensing to autophagy by recruiting the autophagy protein AGT16L1 to the site of pathogen entry.
Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1β production
Production of mature interleukin 1β (IL-1β) requires Il1b transcription and inflammasome-mediated processing of IL-1β protein. Ruland and colleagues show that the RNA virus sensor RIG-I signals via the adaptors CARD9 and Asc to facilitate both processes.
Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines
TLR4 signals via MyD88 and TRIF to activate proinflammatory cytokine and type I interferon responses. Karin and colleagues show that different ubiquitination of TRAF3 via K48 or K63 dictates the ensuing immune response.
Defensins combat pathogenic bacteria invading the mammalian intestine. Salzman and co-workers find that defensins influence the composition of the small intestinal commensal microbiota and the presence of interleukin 17–producing T cells in the lamina propria.
Different routes of bacterial infection induce long-lived TH1 memory cells and short-lived TH17 cells
Naive CD4+ T cells can differentiate into distinct polarized effector cells, but detailed characterization of physiologic CD4 memory is lacking. Jenkins and colleagues show that TH1 and TH17 memory cells differ in longevity and arise via different infection routes.
TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activation
TCR movement in the T cell plasma membrane is not well understood. Using three different types of microscopy, Davis and co-workers identify separate islands of Lat and TCR molecules that concatenate after T cell activation.
An overview, four review articles and two perspective articles cover the cellular and molecular mechanisms required to maintain self tolerance, as well as events that can precipitate tolerance breakdown and lead to autoimmunity.