Resident tissue macrophages (RTMs) have a broad spectrum of immune- and non-immune tissue-supporting activities. More precisely, adipose tissue macrophage (ATM) are phenotypically and functionally heterogeneous populations reflecting the diversity of sub-tissue environments in which they reside. In addition to maintaining   tissue homeostasis and responding to invading pathogens, ATM contribute to numerous metabolic processes at  steady state and disease such as obesity, making them a potential target in clinic.

The focus of our laboratory is to understand the heterogeneity of ATM, their differentiation pathways  and how their sub-tissular niche of residence dictates their tissue specific metabolic functions.

Our approach comprehend technic including single cell and bulk RNA sequencing, together with deep immunophenotyping using multi-parametric (>20 colours)  flow cytometry and Cytometry by Time-Of-Flight (CyTOF). ATM-micro niche interactions will be addressed using high-multiplex imaging approaches such as Hyperion™ Imaging Mass Cytometry and CO-Detection by indexing (CODEX). The integration of this high-dimensional molecular and spatial profiling at single will provide new insights in ATM heterogeneity and refine our understanding of their functional specialization in tissue homeostasis and disease.

Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches.Chakarov S*, Lim HY, Tan L, Lim SY, See P, Lum J, Zhang XM, Foo S, Nakamizo S, Duan K, Kong WT, Gentek R, Balachander A, Carbajo D, Bleriot C, Malleret B, Tam JKC, Baig S, Shabeer M, Toh SES, Schlitzer A, Larbi A, Marichal T, Malissen B, Chen J, Poidinger M, Kabashima K, Bajenoff M, Ng LG, Angeli V, Ginhoux F. Science. 2019 Mar 15;363(6432). pii: eaau0964; doi: 10.1126/science.aau0964.

Role of adipose tissue macrophages in obesity-related disorders. Chakarov S*, Blériot C, Ginhoux F, J. Exp. Med. 2022 Jul 4;219(7):e20211948. doi: 10.1084/jem.20211948

Determinants of resident tissue macrophage form and function. Bleriot C*, Chakarov S*, Ginhoux F#, Immunity 2020 Jun 16 52, 957-970; doi: 10.1016/j.immuni.2020.05.014

Eosinophils in obesity and obesity-associated disorders. Hu Y* and Chakarov S#, Discovery Immunology 2023 Nov 14 Volume 2, Issue 1, 2023, doi: 10.1093/discim/kyad022

Apolipoprotein E controls Dectin-1-dependent development of monocyte-derived alveolar macrophages upon pulmonary β-glucan-induced inflammatory adaptation. Theobald H, Bejarano DA, Katzmarski N, Haub J, Schulte-Schrepping J, Yu J, Bassler K, Ćirović B, Osei-Sarpong C, Piattini F, Vornholz L, Yu X, Sheoran S, Jawazneh A Al, Chakarov S, Haendler K, Brown GD, Williams DL, Bosurgi L, Ginhoux F, Ruland J, Beyer M, Greter M, Kopf M, Schultze JL, Schlitzer A.  Nat Immunol., 2024, 25:994-1006.

Immunomodulatory Leptin Receptor+ Sympathetic Perineurial Cells Protect Against Obesity by Facilitating Neuroendocrine-Mediated Brown Adipose Tissue Thermogenesis. Haberman ER, Sarker G, Arús BA, Yilmaz-Özcan S, Martínez-Sánchez N, Freibergerová E, Fernández-González I, Zentai C, O’Brien CJO, Grainger E, Chakarov S, Raimondi A, Iannacone M, López M, Ginhoux F, Domingos AI, Immunity 2024 Jan 9;57(1):141-152.e5; doi: 10.1016/j.immuni.2023.11.006

Dendritic cell type 3 arises from Ly6C+ monocyte-dendritic cell progenitors. Liu Z, Wang H, Li L, Dress RJ, Zhu Y, Zhang S, De Feo D, Kong WT, Cai P, Shin A, Piot C, Yu J, Gu Y, Zhang M, Gao C, Chen L, Wang H, Vétillard M, Guermonprez P, Kwok I, Ng LG, Chakarov S, Schlitzer A, Becher B, Dutertre CA, Su B, Ginhoux F, Immunity 2023 Aug 8;56(8):1761-1777.e6; doi: 10.1016/j.immuni.2023.07.001

Apolipoprotein E controls Dectin-1-dependent development of monocyte-derived alveolar macrophages upon pulmonary β-glucan-induced inflammatory adaptation. Theobald H, Bejarano DA, Katzmarski N, Haub J, Schulte-Schrepping J, Yu J, Bassler K, Ćirović B, Osei-Sarpong C, Piattini F, Vornholz L, Yu X, Sheoran S, Jawazneh A Al, Chakarov S, Haendler K, Brown GD, Williams DL, Bosurgi L, Ginhoux F, Ruland J, Beyer M, Greter M, Kopf M, Schultze JL, Schlitzer A, BioRxiv 2022 Sep 16; doi: 10.1101/2022.09.15.505390

Dual ontogeny of disease-associated microglia and disease inflammatory macrophages in aging and neurodegeneration. Silvin A, Uderhardt S, Piot C, Da Mesquita S, Yang K, Geirsdottir L, Mulder K, Eyal D, Liu Z, Bridlance, C Thion MS, Zhang XM, Kong WT, Deloger M, Fontes V, Weiner A, Ee R, Dress R, Hang JW, Balachander A, Chakarov S, Malleret B, Dunsmore G, Cexus O, Chen J, Garel S, Dutertre CA, Amit I, Kipnis J, Ginhoux F, Immunity 2022 Aug 9;55(8):1448-1465.e6. doi: 10.1016/j.immuni.2022.07.004

Unravelling the sex-specific diversity and functions of adrenal gland macrophages. Dolfi B, Gallerand A, Firulyova MM, Xu Y, Merlin J, Dumont A, Castiglione A, Vaillant N, Quemener S, Gerke H, Stunault MI, Schrank PR, Kim SH, Zhu A, Ding J, Gilleron J, Magnone V, Barbry P, Dombrowicz D, Duranton C, Wakkach A, Blin-Wakkach C, Becher B, Pagnotta S, Argüello RJ, Rantakari P, Chakarov S, Ginhoux F, Zaitsev K, Kim KW, Yvan-Charvet L, Guinamard RR, Williams JW, Ivanov S, Cell Rep. 2022 Jun 14;39(11):110949. doi: 10.1016/j.celrep.2022.110949

ISM1 protects lung homeostasis via cell-surface GRP78-mediated alveolar macrophage apoptosis. Lam TYW, Nguyen N, Peh HY, Shanmugasundaram M, Chandna R, Tee JT, Ong CB, Hossain MZ, Venugopal S, Zhang T, Xu S, Tao Qiu, Kong WT, Chakarov S, Srivastava S, Liao W, Kim JS, The M, Ginhoux F, Wong FWS, Ge R, PNAS 2022 Jan 25;119(4):e2019161119; doi: 10.1073/pnas.2019161119

A subset of Kupffer cells regulates metabolism through the expression of CD36. Bleriot C, Barreby E, Dunsmore G, Ballaire R, Chakarov S, Ficht X, De Simone G, Andreata F, Fumagalli V, Guo W, Wan G, Gessain G, Khalilnezhad A, Zhang XM, Ang N, Chen P, Morgantini C, Azzimato V, Kong WT, Liu Z, Pai R, Lum J, Shihui F, Low I, Xu C, Malleret B, Mohd Kairi MF, Balachander A, Cexus O, Larbi A, Lee B, Newell EW, Ng LG, Phoo WW, Sobota RM, Sharma A, Howland SW, Jinmiao Chen JM, Bajenoff M, Yvan-Charvet L, Venteclef N, Iannacone M, Aouadi M, and Ginhoux F, Immunity 2021 September 14 54, 1–16; doi: 10.1016/j.immuni.2021.08.006

Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming. De Simone G, Andreata F, Bleriot C, Fumagalli V, Laura C, Garcia-Manteiga JM, Di Lucia P, Gilotto S,  Ficht X, De Ponti FF, Bono EB, Giustini L, Ambrosi G, Mainetti M, Zordan P, Benechet AP, Rava M, Chakarov S, Moalli F, Bajenoff M, Guidotti LG, Florent Ginhoux F and Iannacone M, Immunity 2021 September 14 54, 1–12; doi: 10.1016/j.immuni.2021.05.005

Microbial exposure during early human development primes fetal immune cells. Mishra A, Lai GC, Yao LJ, Aung TT, Shental N, Rotter-Maskowitz A, Shepherdson E, Naranjan Singh G, Pai R, Shanti A, Men Men Wong R, Lee A, Khyriem C, Dutertre CA, Chakarov S, Srinivasan KG, Binte Shadan N, Zhang XM, Khalilnezhad S, Cottier F, Shin Min Tan A, Low G, Chen P, Fan Y, Xiang Hor P, Khoo May Lee A, Choolani M, Vermijlen D, Ankur Sharma A, Fuks G, Straussman R, Pavelka N, Malleret B, McGovern N, Albani S, Kok Yen Chan J, Ginhoux G, Cell 2021 June 24 184, 3394–3409; doi:10.1016/j.cell.2021.04.039

Two populations of self-maintaining monocyte-independent macrophages exist in adult epididymis and testis. Wang M, Yang Y, Cansever D, Wang Y, Kantores C, Messiaen S, Moison D, Livera G, Chakarov S, Weinberger T, Stremmel C, Fijak M, Klein B, Pleuger C, Lian Z, Ma W, Liu O, Klee K, Händler K, Ulas T, Schlitzer A, Schultze JL, Becher B, Greter M, Liu Z, Ginhoux F, Epelman S, Schulz C, Meinhardt A, Bhushan S, PNAS 2021 Jan 5; 118(1) e2013686117; doi: 10.1073/pnas.2013686117

Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinom. Sharma A, Seow J, Dutertre CA, Pai R, Blériot C, Mishra A, Wong R, Singh G, Sudhagar S, Khalilnezhad S, Erdal S, Teo HM, Khalilnezhad A, Chakarov S, Kiat Hon Lim T, Chung Yaw Fui A, Kow Wei Chieh A, Cheow Peng Chung CP, Bonney G, Goh Kim Poh B, Chan J, Chow P, Ginhoux F, DasGupta R, Cell 2020 Oct 15 183, 1–18; doi: 10.1016/j.cell.2020.08.040

Fate mapping via Ms4a3-expression history traces monocyte-derived cells. Liu Z, Gu Y, Chakarov S, Bleriot C, Kwok I, Chen X, Shin A, Huang W, Dress RJ, Dutertre CA, Schlitzer A, Chen J, Ng LG, Wang H, Liu Z, Su B, Ginhoux F. Cell. 2019 Sep 5 178, 1509-1525; doi:10.1016/j.cell.2019.08.009

Non-classical tissue monocytes and two functionally distinct populations of interstitial macrophages populate the mouse lung. Schyns J, Bai O, Ruscitti C, Radermecker C, De Schepper S, Chakarov S, Farnir F, Pirottin D, Ginhoux F, Boeckxstaens G, Bureau F, Marichal T. Nat Commun. 2019 Sep 3; 10:3964; doi: 10.1038/s41467-019-11843-0

Cell-autonomous FLT3L shedding via ADAM10 mediates conventional dendritic cell development in mouse spleen. Fujita K, Chakarov S, Kobayashi T, Sakamoto K, Voisin B, Duan K, Nakagawa T, Horiuchi K, Amagai M, Ginhoux F, Nagao K PNAS. 2019 Jul 16;116(29):14714-14723; doi: 10.1073/pnas.1818907116

Hyaluronan receptor lyve-1-expressing macrophages maintain arterial tone through hyaluronan-mediated regulation of smooth muscle cell collagen. Lim HY, Lim SY, Tan CK, Thiam CH, Goh CC, Carbajo D, Chew SHS, See P, Chakarov S, Wang XN, Lim LH, Johnson LA, Lum J, Fong CY, Bongso A, Biswas A, Goh C, Evrard M, Yeo KP, Basu R, Wang JK, Tan Y, Jain R, Tikoo S, Choong C, Weninger W, Poidinger M, Stanley ER, Collin M, Tan NS, Ng LG, Jackson DG, Ginhoux F, Angeli V Immunity. 2018 Aug 21;49(2):326-341.e7; doi: 10.1016/j.immuni.2018.06.008.

Multiplex peptide-MHC tetramer staining using mass cytometry for deep analysis of the influenza-specific T-cell response in mice. Fehlings M, Chakarov S, Simoni Y, Sivasankar B, Ginhoux G, Newell EW Journal of Immunological Methods 2018 Feb 1; 453:30-36 doi: 10.1016/j.jim.2017.09.010

Induced-pluripotent-stem-cell-derived primitive macrophages provide a platform for modeling tissue-resident macrophage differentiation and function. Takata K, Kozaki T, Lee CZW, Thion MS, Otsuka M, Lim S, Utami KH, Fidan K, Park DS, Malleret B, Chakarov S, See P, Low D, Low G, Garcia-Miralles M, Zeng R, Zhang J, Goh CC, Gul A, Hubert S, Lee B, Chen J, Low I, Shadan NB, Lum J, Wei TS, Mok E, Kawanishi S, Kitamura Y, Larbi A, Poidinger M, Renia L, Ng LG, Wolf Y, Jung S, Önder T, Newell E, Huber T, Ashihara E, Garel S, Pouladi MA, Ginhoux F. Immunity. 2017 Jul 18;47(1):183-198.e6; doi: 10.1016/j.immuni.2017.06.017.

Exposure to bacterial CpG DNA protects from airway allergic inflammation by expanding regulatory lung interstitial macrophages. Sabatel C, Radermecker C, Fievez L, Paulissen G, Chakarov S, Fernandes C, Olivier S, Toussaint M, Pirottin D, Xiao X, Quatresooz P, Sirard JC, Cataldo D, Gillet L, Bouabe H, Desmet CJ, Ginhoux F, Marichal T, Bureau F Immunity. 2017 Mar 21;46(3):457-473; doi: 10.1016/j.immuni.2017.02.016.

Unsupervised high-dimensional analysis aligns dendritic cells across tissues and species. Guilliams M, Dutertre CA, Scott CL, McGovern N, Sichien D, Chakarov S, Van Gassen S, Chen J, Poidinger M, De Prijck S, Tavernier SJ, Low I, Irac SE, Mattar CN, Sumatoh HR, Low GHL, Chung TJK, Chan DKH, Tan KK, Hon TLK, Fossm E, Bogen B, Choolani M, Chan JKY, Larbi A, Luche H, Henri S, Saeys Y, Newell EW, Lambrecht BN, Malissen B, Ginhoux F. Immunity. 2016 Sep 20;45(3):669-684; doi:10.1016/j.immuni.2016.08.015. Epub 2016 Sep13.

Mpath maps multi-branching single-cell trajectories revealing progenitor cell progression during development. Chen J, Schlitzer A, Chakarov S, Ginhoux F, Poidinger M Nat Commun. 2016 Jun 30; 7:11988; doi:10.1038/ncomms11988.

Expansion and activation of CD103(+) dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition. Salmon H, Idoyaga J, Rahman A, Leboeuf M, Remark R, Jordan S, Casanova-Acebes M, Khudoynazarova M, Agudo J, Tung N, Chakarov S, Rivera C, Hogstad B, Bosenberg M, Hashimoto D, Gnjatic S, Bhardwaj N, Palucka AK, Brown BD, Brody J, Ginhoux F, Merad M. Immunity. 2016 Apr 19;44(4):924-38; doi:10.1016/j.immuni.2016.03.012.

Tracking by flow cytometry antigen-specific follicular helper T cells in wild-type animals after protein vaccination. Chakarov S & Fazilleau N Methods Mol Biol. 2015 1291:39-47; doi: 10.1007/978-1-4939-2498-1_4.

Monocyte-derived dendritic cells promote T follicular helper cell differentiation. Chakarov S & Fazilleau N EMBO Mol Med. 2014 May;6(5):590-603; doi: 10.1002/emmm.201403841.