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Distinct Kinase-Independent Role of RIPK3 in CD11c+ Mononuclear Phagocytes in Cytokine-Induced Tissue Repair.

Publication ,  Journal Article
Moriwaki, K; Balaji, S; Bertin, J; Gough, PJ; Chan, FK-M
Published in: Cell Rep
March 7, 2017

Receptor interacting protein kinase 3 (RIPK3) induces necroptosis, a type of regulated necrosis, through its kinase domain and receptor interacting protein (RIP) homotypic interaction motif (RHIM). In addition, RIPK3 has been shown to regulate NLRP3 inflammasome and nuclear factor κB (NF-κB) activation. However, the relative contribution of these signaling pathways to RIPK3-dependent inflammation in distinct immune effectors is unknown. To investigate these questions, we generated RIPK3-GFP reporter mice. We found that colonic CD11c+CD11b+CD14+ mononuclear phagocytes (MNPs) expressed the highest level of RIPK3 in the lamina propria. Consequently, deletion of the RIPK3 RHIM in CD11c+ cells alone was sufficient to impair dextran sodium sulfate (DSS)-induced interleukin (IL)-23 and IL-1β expression, leading to severe intestinal inflammation. In contrast, mice expressing kinase inactive RIPK3 were not hypersensitive to DSS. Thus, a key physiological function of RIPK3 is to promote reparative cytokine expression through intestinal CD11c+ MNPs in a kinase- and necroptosis-independent manner.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

March 7, 2017

Volume

18

Issue

10

Start / End Page

2441 / 2451

Location

United States

Related Subject Headings

  • Wound Healing
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Phagocytes
  • Necrosis
  • Mice, Inbred C57BL
  • Mice
  • Green Fluorescent Proteins
  • Genes, Reporter
  • Gene Deletion
  • Dextran Sulfate
 

Citation

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Moriwaki, K., Balaji, S., Bertin, J., Gough, P. J., & Chan, F.-M. (2017). Distinct Kinase-Independent Role of RIPK3 in CD11c+ Mononuclear Phagocytes in Cytokine-Induced Tissue Repair. Cell Rep, 18(10), 2441–2451. https://doi.org/10.1016/j.celrep.2017.02.015
Moriwaki, Kenta, Sakthi Balaji, John Bertin, Peter J. Gough, and Francis Ka-Ming Chan. “Distinct Kinase-Independent Role of RIPK3 in CD11c+ Mononuclear Phagocytes in Cytokine-Induced Tissue Repair.Cell Rep 18, no. 10 (March 7, 2017): 2441–51. https://doi.org/10.1016/j.celrep.2017.02.015.
Moriwaki K, Balaji S, Bertin J, Gough PJ, Chan FK-M. Distinct Kinase-Independent Role of RIPK3 in CD11c+ Mononuclear Phagocytes in Cytokine-Induced Tissue Repair. Cell Rep. 2017 Mar 7;18(10):2441–51.
Moriwaki, Kenta, et al. “Distinct Kinase-Independent Role of RIPK3 in CD11c+ Mononuclear Phagocytes in Cytokine-Induced Tissue Repair.Cell Rep, vol. 18, no. 10, Mar. 2017, pp. 2441–51. Pubmed, doi:10.1016/j.celrep.2017.02.015.
Moriwaki K, Balaji S, Bertin J, Gough PJ, Chan FK-M. Distinct Kinase-Independent Role of RIPK3 in CD11c+ Mononuclear Phagocytes in Cytokine-Induced Tissue Repair. Cell Rep. 2017 Mar 7;18(10):2441–2451.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

March 7, 2017

Volume

18

Issue

10

Start / End Page

2441 / 2451

Location

United States

Related Subject Headings

  • Wound Healing
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Phagocytes
  • Necrosis
  • Mice, Inbred C57BL
  • Mice
  • Green Fluorescent Proteins
  • Genes, Reporter
  • Gene Deletion
  • Dextran Sulfate