Matteoli, Gianluca

In our research group, we aim to investigate the role of macrophages (Mφs) during the resolution phase of intestinal inflammation, in particular using standardized models of colitis and of postoperative ileus. Preliminary data collected by our group suggest that resolution of inflammation during intestinal inflammation is dependent upon a specific subpopulation of monocyte-derived Mφs with a pro-resolving phenotype. Lack of this population of "regulatory" myeloid cells results in prolonged inflammation, increased microscopic lesions and altered gastrointestinal motility. We hypothesize that monocyte-derived Mφs with pro-resolving capacity may play a crucial role in “re-educating” the intestinal microenvironment and in restoring tissue homeostasis after inflammation. Thus, the main goal of our research is to evaluate the phenotype and function of pro-resolving monocyte-derived Mφs during intestinal inflammation, and to investigate the molecules and pathways involved in their generation. Identification of new molecules and pathways involved in the differentiation and accumulation of Mφs with a pro-resolving phenotype during intestinal inflammation will represent a major breakthrough in elucidating the pathogenesis of inflammatory bowel disease (IBD) and will potentially give rise to a new class of molecules to treat and/or favor remission in IBD patients.

Technology available:

  • In vitro cell-cell interaction experiments using immune cells and/or enteric neurons or glial cells isolated from mouse and patients
  • Isolation and characterization of murine and/or human primary cells including macrophages, lymphocytes, enteric neurons and glial cells from the intestinal wall of mouse and patients via multicolor cell sorting and qPCR
  • Confocal microscopy
  • Live calcium imaging to monitor macrophages response in tissue
  • Optogenetic to activate the enteric nervous system and study macrophages response

Key publications related to Mye-EUNITER:

  1. Van Bree SH, Gomez-Pinilla PJ, van de Bovenkamp FS, Di Giovangiulio M, Farro G, Nemethova A, Cailotto C, de Jonge WJ, Lee K, Ramirez-Molina C, Lugo D, Skynner MJ, Boeckxstaens GE, Matteoli G#. Inhibition of spleen tyrosine kinase as treatment of postoperative ileus. Gut. 2013 Nov;62(11):1581-90. #Corresponding author.
  2. Di Giovangiulio M, Stakenborg N, Bosmans G, Meroni E, Farro G, Gomez-Pinilla PJ, Depoortere I, Boeckxstaens GE, Matteoli G#.. Ghrelin receptor modulates T helper cells during intestinal inflammation. Neurogastroenterol Motil. 2015 Nov;27(11):1542-52 #Corresponding author.
  3. Frittoli E#, Matteoli G#, Palamidessi A, Mazzini E, Maddaluno L, Disanza A, Yang C, Svitkina T, Rescigno M, Scita G. The signaling adaptor Eps8 is an essential actin capping protein for dendritic cell migration. Immunity. 2011 Sep 23;35(3):388-99; #Co-first author.
  4. Matteoli G, Gomez-Pinilla PJ, Nemethova A, Di Giovangiulio M, Cailotto C, van Bree SH, Michel K, Tracey KJ, Schemann M, Boesmans W, Vanden Berghe P, Boeckxstaens GE. A distinct vagal anti-inflammatory pathway modulates intestinal muscularis resident macrophages independent of the spleen. Gut. 2014 Jun;63(6):938-48.
  5. Matteoli G, Mazzini E, Iliev ID, Mileti E, Fallarino F, Puccetti P, Chieppa M, Rescigno M. Gut CD103+ dendritic cells express indoleamine 2,3-dioxygenase which influences T regulatory/T effector cell balance and oral tolerance induction. Gut. 2010 May;59(5):595-604.