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URMC / Labs / Elliott Lab / Projects / Find-Me Signals in Cell Clearance and Immunity

Find-Me Signals in Cell Clearance and Immunity

Cells undergoing apoptosis release soluble cues called “find-me” signals that promote the recruitment of phagocytes and aid in the phagocytic clearance of dying cells. Triphosphate nucleotides (ATP and UTP), acting via P2Y receptors on phagocytes, were recently identified as such a find-me cue. In addition to acting as recruitment signals, we have found that ATP released by apoptotic cells can drive a powerful anti-inflammatory response in macrophages via the CD73-dependent activation of the A2a and A2b adenosine receptors. Current studies are underway to further understand the molecular regulation and physiologic consequences of find-me signaling in multiple aspects of immune-related diseases, including inflammation, fibrosis, HIV-1 infection and cancer immunotherapy.

murine thymus
Identification of dying cells (TUNEL+(red)) in the murine thymus along with cortical epithelial cells (cytokeratin(green)).

RELEVANT PUBLICATIONS

  1. Murphy PS, Wang J, Bhagwat SP, Munger JC, Janssen WJ, Wright TW, Elliott MR. CD73 regulates anti-inflammatory signaling between apoptotic cells and endotoxin-conditioned tissue macrophages. Cell Death Differ. 2017 Mar;24(3):559-570. PubMed PMID: 28060378; PubMed Central PMCID: PMC5344214.
  2. Chekeni FB, Elliott MR, Sandilos JK, Walk SF, Kinchen JM, Lazarowski ER, Armstrong AJ, Penuela S, Laird DW, Salvesen GS, Isakson BE, Bayliss DA, Ravichandran KS. Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature. 2010 Oct 14;467(7317):863-7. PubMed PMID: 20944749; PubMed Central PMCID: PMC3006164.
  3. Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, Park D, Woodson RI, Ostankovich M, Sharma P, Lysiak JJ, Harden TK, Leitinger N, Ravichandran KS. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature. 2009 Sep 10;461(7261):282-6. PubMed PMID: 19741708; PubMed Central PMCID: PMC2851546.