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Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183.

Cell Rep. 2018 Jun 26;23(13):3750-3758
Coco Chu 1 , Saya Moriyama 1 , Zhi Li 2 , Lei Zhou 3 , Anne-Laure Flamar 1 , Christoph S N Klose 1 , Jesper B Moeller 4 , Gregory G Putzel 1 , David R Withers 2 , Gregory F Sonnenberg 3 , David Artis 5
Coco Chu 1 , Saya Moriyama 1 , Zhi Li 2 , Lei Zhou 3 , Anne-Laure Flamar 1 , Christoph S N Klose 1 , Jesper B Moeller 4 , Gregory G Putzel 1 , David R Withers 2 , Gregory F Sonnenberg 3 , David Artis 5
+ et al

[No authors listed]

Author information
  • 1 Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
  • 2 Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
  • 3 Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
  • 4 Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Department of Molecular Medicine, University of Southern Denmark, Odense 5000, Denmark.
  • 5 Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA. Electronic address: dartis@med.cornell.edu.

摘要

The intestinal tract is constantly exposed to various stimuli. Group 3 innate lymphoid cells (ILC3s) reside in lymphoid organs and in the intestinal tract and are required for immunity to enteric bacterial infection. However, the mechanisms that regulate the ILC3s in vivo remain incompletely defined. Here, we show that GPR183, a chemotactic receptor expressed on murine and human ILC3s, regulates ILC3 migration toward its ligand 7α,25-dihydroxycholesterol (7α,25-OHC) in vitro, and GPR183 deficiency in vivo leads to a disorganized distribution of ILC3s in mesenteric lymph nodes and decreased ILC3 accumulation in the intestine. GPR183 functions intrinsically in ILC3s, and GPR183-deficient mice are more susceptible to enteric bacterial infection. Together, these results reveal a role for the GPR183-7α,25-OHC pathway in regulating the accumulation, distribution, and anti-microbial and tissue-protective functions of ILC3s and define a critical role for this pathway in promoting innate immunity to enteric bacterial infection.

KEYWORDS: GPR183, accumulation, anti-microbial, distribution, group 3 innate lymphoid cells, intestine, mesenteric lymph node

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