The aim of this project is to design apoptotic cell clearance based approaches to improve the resolution of inflammation. We have identified several mechanisms that confer peritoneal macrophages with an extraordinary efficiency clearing dead cells through phagocytosis. The use of MARCO-deficient mice revealed a tissue-specific regulation of efferocytosis in peritoneal macrophages. Based on those results, we have genetically engineered ER-HoxB8 cell lines overexpressing MARCO, which show a higher potential of phagocytosis. Moreover, comparative analysis of tissue-resident macrophages revealed diverse regulatory patterns of other phagocytic receptors in response to bacterial triggers. Therefore, our current focus is to study receptor engagement in tissue-resident macrophages during acute inflammation, analysing its role in efferocytosis and tissue repair. Combined with a multiscale imaging approach in mouse models of acute inflammation, we will elucidate the mechanisms of efferocytosis-mediated inflammatory resolution in an organ-specific manner.
The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.
2024
Aranda-Pardos I, Imam-Chasan A, Alonso-Gonzalez N. Studying Efferocytosis Dynamics in Tissue-Resident Macrophages Ex Vivo. Methods Mol Biol 2024;2713: 389-405. Abstract
Liebold I, Al Jawazneh A, Casar C, Lanzloth C, Leyk S, Hamley M, Wong MN, Kylies D, Gräfe SK, Edenhofer I, Aranda-Pardos I, Kriwet M, Haas H, Krause J, Hadjilaou A, Schromm AB, Richardt U, Eggert P, Tappe D, Weidemann SA, Ghosh S, Krebs CF, A-Gonzalez N, Worthmann A, Lohse AW, Huber S, Rothlin CV, Puelles VG, Jacobs T, Gagliani N, Bosurgi L. Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages. Science 2024;384: eabo7027. Abstract
2020
Nicolas-Avila JA, Lechuga-Vieco AV, Esteban-Martinez L, Sanchez-Diaz M, Diaz-Garcia E, Santiago DJ, Rubio-Ponce A, Li JLY, Balachander A, Quintana JA, Martinez-de-Mena R, Castejon-Vega B, Pun-Garcia A, Traves PG, Bonzon-Kulichenko E, Garcia-Marques F, Cusso L, A-Gonzalez N, Gonzalez-Guerra A, Roche-Molina M, Martin-Salamanca S, Crainiciuc G, Guzman G, Larrazabal J, Herrero-Galan E, Alegre-Cebollada J, Lemke G, Rothlin CV, Jimenez-Borreguero LJ, Reyes G, Castrillo A, Desco M, Munoz-Canoves P, Ibanez B, Torres M, Ng LG, Priori SG, Bueno H, Vazquez J, Cordero MD, Bernal JA, Enriquez JA, Hidalgo A. A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart. Cell 2020;183: 94-109.e23. Abstract
2019
Rauschmeier R, Gustafsson C, Reinhardt A, Alonso Gonzalez N, Tortola L, Cansever D, Subramanian S, Taneja R, Rossner MJ, Sieweke MH, Greter M, Månsson R, Busslinger M, Kreslavsky T. Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity. Embo J 2019;38: e101233. Abstract
2017
A-Gonzalez N, Quintana JA, Garcia-Silva S, Mazariegos M, Gonzalez de la Aleja A, Nicolas-Avila JA, Walter W, Adrover JM, Crainiciuc G, Kuchroo VK, Rothlin CV, Peinado H, Castrillo A, Ricote M, Hidalgo A. Phagocytosis imprints heterogeneity in tissue-resident macrophages. J Exp Med 2017;214: 1281-1296. Abstract
2014
A-Gonzalez N, Hidalgo A. Nuclear Receptors and Clearance of Apoptotic Cells: Stimulating the Macrophage's Appetite. Front Immunol 2014;5: 211. Abstract
2009
A-Gonzalez N, Bensinger SJ, Hong C, Beceiro S, Bradley MN, Zelcer N, Deniz J, Ramirez C, Diaz M, Gallardo G, de Galarreta CR, Salazar J, Lopez F, Edwards P, Parks J, Andujar M, Tontonoz P, Castrillo A. Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity 2009;31: 245-258. Abstract
