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T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis
Clinical and Experimental Immunology
  • R. V. Anantha, Schulich School of Medicine & Dentistry
  • D. M. Mazzuca, Schulich School of Medicine & Dentistry
  • S. X. Xu, Schulich School of Medicine & Dentistry
  • S. A. Porcelli, Albert Einstein College of Medicine of Yeshiva University
  • D. D. Fraser, Children's Health Research Institute, London, ON
  • C. M. Martin, London Health Sciences Centre
  • I. Welch, Schulich School of Medicine & Dentistry
  • T. Mele, Schulich School of Medicine & Dentistry
  • S. M.M. Haeryfar, Schulich School of Medicine & Dentistry
  • J. K. Mccormick, Schulich School of Medicine & Dentistry
Document Type
Article
Publication Date
11-1-2014
URL with Digital Object Identifier
10.1111/cei.12404
Abstract

Summary: Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNKT) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of iNKT cells in their peripheral blood (as a percentage of their circulating T cells) compared to non-septic patients. We therefore investigated the role of iNKT cells in a mouse model of intra-abdominal sepsis (IAS). Our data show that iNKT cells are pathogenic in IAS, and that T helper type 2 (Th2) polarization of iNKT cells using the synthetic glycolipid OCH significantly reduces mortality from IAS. This reduction in mortality is associated with the systemic elevation of the anti-inflammatory cytokine interleukin (IL)-13 and reduction of several proinflammatory cytokines within the spleen, notably interleukin (IL)-17. Finally, we show that treatment of sepsis with OCH in mice is accompanied by significantly reduced apoptosis of splenic T and B lymphocytes and macrophages, but not natural killer cells. We propose that modulation of iNKT cell responses towards a Th2 phenotype may be an effective therapeutic strategy in early sepsis.

Citation Information
R. V. Anantha, D. M. Mazzuca, S. X. Xu, S. A. Porcelli, et al.. "T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis" Clinical and Experimental Immunology Vol. 178 Iss. 2 (2014) p. 292 - 309
Available at: http://works.bepress.com/douglas-fraser/48/