Research

Dendritic Cell and Macrophage Ontogeny

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florent_ginhoux@immunol.a-star.edu.sg

Florent Ginhoux


Florent Ginhoux graduated in Biochemistry from the University Pierre et Marie CURIE (UPMC), Paris VI, obtained a Masters degree in Immunology from the Pasteur Institute in 2000 and his PhD in 2004 from UPMC, Paris VI.  As a postdoctoral fellow, he joined the Laboratory of Miriam Merad in the Mount Sinai School of Medicine (MSSM), New York. In 2008, he became an Assistant Professor in the Department of Gene and Cell Medicine, MSSM and member of the Immunology Institute of MSSM. He joined the Singapore Immunology Network (SIgN), A*STAR in May 2009 as a Junior Principal Investigator. He is now a Senior Principal Investigator and an EMBO Young Investigator and his laboratory is focusing on the ontogeny and differentiation of macrophages and dendritic cells in both humans and mice. Relevant to skin research, he is now particularly interested in studying dendritic cells and macrophages in T-cell mediated skin disorders and to determine their role in regulating cutaneous tolerance and immunity.


Dendritic cells (DCs), monocytes and macrophages play crucial and distinct roles in tissue homeostasis and immunity, but also contribute to a broad spectrum of pathologies and are thus attractive therapeutic targets. Potential intervention strategies aiming at manipulation of these cells will require in-depth insights of their origins and the mechanisms that govern their homeostasis.

The focus of the laboratory is to understand the ontogeny of DCs, monocytes and macrophages, their differentiation pathways and how their unique ontogeny dictates their immune functions. Our approach encompasses the integration of high dimensional platforms such as RNAseq, single cell transcriptome analysis using microfluidic RNA sequencing and deep immunophenotypic assessment using state of the art 18 parameters flow cytometry or Cytometry by Time-Of-Flight mass spectrometry (CyTOF) (In collaboration with Dr Evan Newell, SIgN). Such high density molecular profiling at the single level and at unprecedented dimensionality and complexity will provide new insights in the biology of DC, monocyte and macrophage cell populations. Defining macrophage and DC populations on the criteria of their origin may aid our understanding of their discrete roles in tissue immunity and homeostasis, as ontogeny of DC and macrophage subsets likely underlie their functional specializations.

Relevant to skin research, he is now particularly interested in studying DCs and macrophages in T-cell mediated skin disorders and to determine their role in regulating cutaneous tolerance and immunity. In collaboration with Dr Mark Tang from the Skin Centre, Singapore, he is characterizing in details their phenotype, morphology and frequency as well as specialized functional properties in Atopic Dermatitis and Psoriasis. Another project, in collaboration with L’Oreal, aims to define DCs and macrophages in photo-aged Asian skin. 

Group Members

Research Fellows Svetoslav CHAKAROV

Andreas SCHLITZER

Naomi MCGOVERN
  Baptiste JANELA (GALDERMA Collaboration)
  Shawn LIM (L'Oreal Collaboration)
Visiting Scientists Kazayuki TAKATA, Kyoto Pharmaceutical University

Charles-Antoine DUTERTRE, DUKE-NUS Program in Emerging Disease
PhD Students Donovan LOW
  Peter SEE
  Francisca de ALMEIDA
Research Officers
Masayuki OTSUKA
  Gillian LOW

Kern Rei Chng, Angeline Su Ling Tay, Chenhao Li, Amanda Hui Qi Ng, Jingjing Wang, Bani Kaur Suri, Sri Anusha Matta, Naomi McGovern, Baptiste Janela, Xuan Fei Colin C. Wong, Yang Yie Sio, Bijin Veonice Au, Andreas Wilm, Paola Florez De Sessions, Thiam Chye Lim, Mark Boon Yang Tang, Florent Ginhoux, John E. Connolly, E. Birgitte Lane, Fook Tim Chew, John E. A. Common & Niranjan Nagarajan. Whole metagenome profiling reveals skin microbiome-dependent susceptibility to atopic dermatitis flare. Nature Microbiology 2016;1:16106. doi:10.1038/nmicrobiol.2016.106 Link
Heymann F, Peusquens J, Ludwig-Portugall I, Kohlhepp M, Ergen C, Niemietz P, Martin C, van Rooijen N, Ochando JC, Randolph GJ, Luedde T, Ginhoux F, Kurts C, Trautwein C, Tacke F. Liver inflammation abrogates immunological tolerance induced by Kupffer cells. Hepatology. 2015 Mar 21. doi: 10.1002/hep.27793. Link
Gunawan M, Venkatesan N, Loh JT, Wong JF, Berger H, Neo WH, Li LY, La Win MK, Yau YH, Guo T, See PC, Yamazaki S, Chin KC, Gingras AR, Shochat SG, Ng LG, Sze SK, Ginhoux F, Su IH. The methyltransferase Ezh2 controls cell adhesion and migration through direct methylation of the extranuclear regulatory protein talin. Nat Immunol. 2015 Mar 9. doi: 10.1038/ni.3125. Link
Ginhoux F and Prinz M. Origin of Microglia: Currents Concepts and Past Controversies. CSH Perspectives "Glia" monograph.
Li L, Ng DS, Mah W, Almeida FF, Rahmat SA, Rao VK, Leow SC, Laudisi F, Peh MT, Goh AM, Lim JS, Wright GD, Mortellaro A, Taneja R, Ginhoux F, Lee CG, Moore PK, Lane DP. A unique role for p53 in the regulation of M2 macrophage polarization. Cell Death Differ. 2014 Dec 19. doi: 10.1038/cdd.2014.212. Link
Evrard M, Chong SZ, Devi S, Chew WK, Lee B, Poidinger M, Ginhoux F, Tan SM, Ng LG. Visualization of bone marrow monocyte mobilization using Cx3cr1gfp/+Flt3L-/- reporter mouse by multiphoton intravital microscopy. J Leukoc Biol. 2015 Mar;97(3):611-9. doi: 10.1189/jlb.1TA0514-274R. Link
Hoeffel G, Squarzoni P, Garel S and Ginhoux F. Microglial ontogeny and functions in shaping brain circuits: implication for CNS developmental diseases. Book chapter “Macrophages: Biology and Role in the Pathology of Diseases (SPRINGER)”.
Cerny D, Haniffa M, Shin A, Bigliardi P, Tan BK, Lee B, Poidinger M, Tan EY, Ginhoux F, Fink K. Selective susceptibility of human skin antigen presenting cells to productive dengue virus infection. PLoS Pathog. 2014 Dec 4;10(12):e1004548. doi: 10.1371/journal.ppat.1004548. Link
Goh CC, Li JL, Devi S, Bakocevic N, See P, Larbi A, Weninger W, Ginhoux F, Angeli V, Ng LG. Real-time imaging of dendritic cell responses to sterile tissue injury. J Invest Dermatol. 2015 Apr;135(4):1181-4. doi: 10.1038/jid.2014.506. Link
Malleret B, Li A, Zhang R, Tan KS, Suwanarusk R, Claser C, Cho JS, Koh EG, Chu CS, Pukrittayakamee S, Ng ML, Ginhoux F, Ng LG, Lim CT, Nosten F, Snounou G, Rénia L, Russell B. Plasmodium vivax: restricted tropism and rapid remodeling of CD71-positive reticulocytes. Blood. 2015 Feb 19;125(8):1314-24. doi: 10.1182/blood-2014-08-596015. Link
Ginhoux F. Fate PPAR-titioning: PPAR-γ 'instructs' alveolar macrophage development. Nat Immunol. 2014 Nov;15(11):1005-7. doi: 10.1038/ni.3011. Link
McGovern N, Chan JK, Ginhoux F. Dendritic cells in humans--from fetus to adult. Int Immunol. 2015 Feb;27(2):65-72. doi: 10.1093/intimm/dxu091. Link
Becher B, Schlitzer A, Chen J, Mair F, Sumatoh HR, Teng KW, Low D, Ruedl C, Riccardi-Castagnoli P, Poidinger M, Greter M, Ginhoux F, Newell EW. High-dimensional analysis of the murine myeloid cell system. Nat Immunol. 2014 Dec;15(12):1181-9. doi: 10.1038/ni.3006. Link
Dutertre CA, Wang LF, Ginhoux F. Aligning bona fide dendritic cell populations across species. Cell Immunol. 2014 Sep-Oct;291(1-2):3-10. doi: 10.1016/j.cellimm.2014.08.006. Link
McGovern N, Schlitzer A, Gunawan M, Jardine L, Shin A, Poyner E, Green K, Dickinson R, Wang XN, Low D, Best K, Covins S, Milne P, Pagan S, Aljefri K, Windebank M, Miranda-Saavedra D, Larbi A, Wasan PS, Duan K, Poidinger M, Bigley V, Ginhoux F, Collin M, Haniffa M. Human dermal CD14⁺ cells are a transient population of monocyte-derived macrophages. Immunity. 2014 Sep 18;41(3):465-77. doi: 10.1016/j.immuni.2014.08.006. Link
Squarzoni P, Oller G, Hoeffel G, Pont-Lezica L, Rostaing P, Low D, Bessis A, Ginhoux F, Garel S. Microglia modulate wiring of the embryonic forebrain. Cell Rep. 2014 Sep 11;8(5):1271-9. doi: 10.1016/j.celrep.2014.07.042. Link
Alexander KA, Flynn R, Lineburg KE, Kuns RD, Teal BE, Olver SD, Lor M, Raffelt NC, Koyama M, Leveque L, Le Texier L, Melino M, Markey KA, Varelias A, Engwerda C, Serody JS, Janela B, Ginhoux F, Clouston AD, Blazar BR, Hill GR, MacDonald KP. CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease. J Clin Invest. 2014 Oct;124(10):4266-80. doi: 10.1172/JCI75935. Link
Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N, Schraml BU, Segura E, Tussiwand R, Yona S. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol. 2014 Aug;14(8):571-8. doi: 10.1038/nri3712. Link
Zhou Q, Ho AW, Schlitzer A, Tang Y, Wong KH, Wong FH, Chua YL, Angeli V, Mortellaro A, Ginhoux F, Kemeny DM. GM-CSF-licensed CD11b+ lung dendritic cells orchestrate Th2 immunity to Blomia tropicalis. J Immunol. 2014 Jul 15;193(2):496-509. doi: 10.4049/jimmunol.1303138. Link
Ginhoux F, Jung S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol. 2014 Jun;14(6):392-404. doi: 10.1038/nri3671. Link
Ginhoux F, Schlitzer A. CD11b+ DCs rediscovered: implications for vaccination. Expert Rev Vaccines. 2014 Apr;13(4):445-7. doi: 10.1586/14760584.2014.893196. Link
Schlitzer A, Ginhoux F. Organization of the mouse and human DC network. Curr Opin Immunol. 2014 Feb;26:90-9. doi: 10.1016/j.coi.2013.11.002. Link
Bakocevic N, Claser C, Yoshikawa S, Jones LA, Chew S, Goh CC, Malleret B, Larbi A, Ginhoux F, de Lafaille MC, Karasuyama H, Renia L, Ng LG. CD41 is a reliable identification and activation marker for murine basophils in the steady state and during helminth and malarial infections. Eur J Immunol. 2014 Jun;44(6):1823-34. doi: 10.1002/eji.201344254. Link