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Turley SJ, Lee JW, Dutton-Swain N, et al. Endocrine self and gut nonself intersect in the pancreatic lymph nodes

Section on Immunology and Immunogenetics, Joslin Diabetes Center, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 01/2006; 102(49):17729-33. DOI: 10.1073/pnas.0509006102
Source: PubMed

ABSTRACT The autoimmune cascade that culminates in diabetes initiates within pancreatic lymph nodes (PLNs). Here, we show that developmentally controlled lymphogenesis establishes a preferential trafficking route from the gut to the PLN, where T cells can be activated by antigens drained from the peritoneum and the gastrointestinal tract. Furthermore, intestinal stress modifies the presentation of pancreatic self-antigens in PLNs. The convergence of endocrine and intestinal contents within PLNs has significant implications for type 1 diabetes and may help to explain the link between autoimmune pathogenesis and environmental provocation.

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Available from: Shannon J Turley, Dec 12, 2014
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    • "Gut microbiota has been in recent focus as an environmental factor regulating autoimmunity in type 1 diabetes (Dunne et al., 2014; Karlsson et al., 2013). Potential mechanisms by which microbiota and gut immune responses to microbes could link to diabetic autoimmunity are presentation of gut antigens with molecular mimicry to islet antigens to naïve T cells in pancreatic lymph node (PaLN), or bystander activation of steady-state dendritic cells presenting islet antigens cells in PaLN (Turley et al., 2005). Gut-specific T-cell clones expanding in PaLN could home in pancreatic islets (Hanninen et al., 2007) and, in case of molecular mimicry, participate in islet destruction. "
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    • "Utilization of the Salmonella pathogenicity island-2 (SPI2)- encoded type III secretion system (T3SS) [25] for antigen delivery delays antigen expression until the bacteria are taken up by APCs, which increases safety and efficacy. The APCs process and present antigen to other immune cells in the gut and then migrate to other organs [26] [27]. Such vaccines have been shown to be very effective in eliciting both CD8 and CD4 T cell-mediated immune responses in models of infectious diseases and cancer [28] [29]. "
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    • "The pancreatic lymph nodes (PLNs), mesenteric lymph nodes draining pancreatic tissues, are important sites for the induction of gut-driven immune responses, as demonstrated by the ability of DCs loaded with orally administered ovalbumin to prime both OT-I and OT-II TCR-transgenic cells in the PLNs [41] "
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