Biologie de l’inflammation – CIML

Recherche

Thème

Immunologie intégrative des lymphocytes B

Tolérance immunitaire et différenciation des cellules T

Membres

Directeur(trice) de Recherche

Berengere DE LAVAL

Chargé(e) de Recherche

Marjorie FRANCOIS

Ingénieur(e) d’Etude

Etudiant(e) en thèse

Ingénieur(e) de Recherche

Lucas RUFFINATTO

Etudiant(e) en thèse

Sandrine SARRAZIN

Chargé(e) de Recherche

Jean-Pierre GORVEL

Directeur(trice) de Recherche

Chargé(e) de Recherche

À propos

Immunobiology of Mononuclear Phagocytes

The Lawrence lab studies macrophages and dendritic cells and their roles in cancer. We use sophisticated genetic mouse models and high dimensional proteomic and genomic analysis at single cell and spatial resolution to understand the roles these cells play in shaping the tumour microenvironment and it’s impact on tumour growth and response to therapy. Our previous work has identified macrophage and dendritic cell subsets with pro and anti-tumoral functions and we have mapped molecular pathways that drive their functional polarisation within the tumour microenvironment. We continue to dissect the molecular pathways and cellular mechanisms that drive the functional diversification of these cells with the aim to identify targets for therapeutic intervention.

Hematopoiesis and Inflammation

The HSC group joined the Lawrence lab in January 2024, we focus on hematopoietic stem cells and macrophages. The work carried out by Sandrine Sarrazin and Bérengère De Laval explores how hematopoietic stem cells commit to the myeloid lineage, sense pathogens, and establish immune memory, uncovering previously unknown functions in immune responses. Simultaneously, the group explores self-renewal and reprogramming processes in macrophages, examining their roles in inflammation, tissue regeneration, and cancer. This research aims to deepen our understanding of the connections between hematopoietic development,

Actualités

Sandrine SARRAZIN, exploratrice de l'immunité, passeuse de savoir

Sandrine Sarrazin, chargée de recherche Inserm au CIML, est mise en lumière dans le magazine de l’Inserm du mois d’Octobre. […]

Projets

HSC-Immunobiography

Project : HSC-Immunobiography Mon objectif est de comprendre comment les stress inflammatoires rencontrés au cours de la vie d’un individu […]

Berengere DE LAVAL

From HSC to macrophages and back

Project : HematoMaf Bien que les cellules souches hématopoïétiques (CSH) soient utilisées en thérapie cellulaire chez l’humain depuis plus de 40 ans, […]

Sandrine SARRAZIN

International Research Project: Rôle thérapeutique des macrophages en oncologie et régénération

Project : CureMAC Ce projet de recherche franco-allemand, coordonné par Sandrine Sarrazin, associe les expertises de son groupe avec celles des équipes […]

Sandrine SARRAZIN

Publications

Huang R, Wang Y, Teng H, Xu M, He K, Shen Y, Guo G, Feng X, Li T, Zhou B, Bajenoff M, Lawrence T, Li..., Tyrosinase in melanoma inhibits anti-tumor activity of PD-1 deficient T cells., BMC Biol 2025 May; 23(1): 135.

Wang Y, Dowling SD, Rodriguez V, Maciuch J, Mayer M, Therron T, Shaw TN, Gurra MG, Shah CL, Makinde ..., Comprehensive analysis of myeloid reporter mice., bioRxiv 2025 Feb; (): .

Zhou B, Liu Y, Ma H, Zhang B, Lu B, Li S, Liu T, Qi Y, Wang Y, Zhang M, Qiu J, Fu R, Li W, Lu L, Tia..., Zdhhc1 deficiency mitigates foam cell formation and atherosclerosis by inhibiting PI3K-Akt-mTOR signaling pathway through facilitating the nuclear translocation of p110α., Biochim Biophys Acta Mol Basis Dis 2025 Feb; 1871(2): 167577.

Alraies Z, Rivera CA, Delgado MG, Sanséau D, Maurin M, Amadio R, Maria Piperno G, Dunsmore G, Yatim..., Cell shape sensing licenses dendritic cells for homeostatic migration to lymph nodes., Nat Immunol 2024 Jul; 25(7): 1193-1206.

Kandalla PK, Subburayalu J, Cocita C, de Laval B, Tomasello E, Iacono J, Nitsche J, Canali MM, Catho..., M-CSF directs myeloid and NK cell differentiation to protect from CMV after hematopoietic cell transplantation., EMBO Mol Med 2023 Nov; 15(11): e17694.

Anstee JE, Feehan KT, Opzoomer JW, Dean I, Muller HP, Bahri M, Cheung TS, Liakath-Ali K, Liu Z, Choy..., LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer., Dev Cell 2023 Sep; 58(17): 1548-1561.e10.

Zhang L, Feng X, Shen Y, Wang Y, Liu Z, Ma Y, Gu Y, Guo G, Duan L, Lu L, Liang Y, Lawrence T, Huang ..., A novel ZsGreen knock-in melanoma cell line reveals the function of CD11b in tumor phagocytosis., Immunol Cell Biol 2022 Oct; 100(9): 691-704.

Guillot J, Dominici C, Lucchesi A, Nguyen HTT, Puget A, Hocine M, Rangel-Sosa MM, Simic M, Nigri J, ..., Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer., Nat Commun 2022 Apr; 13(1): 1985.

Benoit-Lizon I, Jacquin E, Rivera Vargas T, Richard C, Roussey A, Dal Zuffo L, Martin T, Melis A, Vi..., CD4 T cell-intrinsic STING signaling controls the differentiation and effector functions of TH1 and TH9 cells., J Immunother Cancer 2022 Jan; 10(1): .

Julie Rebejac, Elisa Eme-Scolan, Laurie Arnaud Paroutaud, Sarah Kharbouche, Matei Teleman, Lionel Sp..., Meningeal macrophages protect against viral neuroinfection, <i>Immunity</i>, 2022, 55 (11), pp.2103-2117.e10. <a target="_blank" href="https://dx.doi.org/10.1016/j.immuni.2022.10.005">⟨10.1016/j.immuni.2022.10.005⟩</a>.

Gu Y, Lawrence T, Mohamed R, Liang Y, Yahaya BH, The emerging roles of interstitial macrophages in pulmonary fibrosis: A perspective from scRNA-seq analyses., Front Immunol 2022 ; 13(): 923235.

Opzoomer JW, Anstee JE, Dean I, Hill EJ, Bouybayoune I, Caron J, Muliaditan T, Gordon P, Sosnowska D..., Macrophages orchestrate the expansion of a proangiogenic perivascular niche during cancer progression., Sci Adv 2021 Nov; 7(45): eabg9518.

Chao T, Lu L, Zhang L, Huang R, Liu Z, Zhou B, Kong E, Zhang Z, Lawrence T, Liang Y, An inducible model for specific neutrophil depletion by diphtheria toxin in mice., Sci China Life Sci 2021 Aug; 64(8): 1227-1235.

Ghislat G, Cheema AS, Baudoin E, Verthuy C, Ballester PJ, Crozat K, Attaf N, Dong C, Milpied P, Mali..., NF-κB-dependent IRF1 activation programs cDC1 dendritic cells to drive antitumor immunity., Sci Immunol 2021 Jul; 6(61): .

Wilkinson H, Leonard H, Chen D, Lawrence T, Robson M, Goossens P, McVey JH, Dorling A, PAR-1 signaling on macrophages is required for effective in vivo delayed-type hypersensitivity responses., iScience 2021 Jan; 24(1): 101981.

Zhou B, Lawrence T, Liang Y, The Role of Plasmacytoid Dendritic Cells in Cancers., Front Immunol 2021 ; 12(): 749190.

Etzerodt A, Moulin M, Doktor TK, Delfini M, Mossadegh-Keller N, Bajenoff M, Sieweke MH, Moestrup SK,..., Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer., J Exp Med 2020 Apr; 217(4): .

Tilstam PV, Soppert J, Hemmers C, Harlacher E, Döring Y, van der Vorst EPC, Schulte C, Alampour-Raj..., Non-activatable mutant of inhibitor of kappa B kinase α (IKKα) exerts vascular site-specific effects on atherosclerosis in Apoe-deficient mice., Atherosclerosis 2020 Jan; 292(): 23-30.

Huang R, Guo G, Lu L, Fu R, Luo J, Liu Z, Gu Y, Yang W, Zheng Q, Chao T, He L, Wang Y, Niu Z, Wang H..., The three members of the Vav family proteins form complexes that concur to foam cell formation and atherosclerosis., J Lipid Res 2019 Dec; 60(12): 2006-2019.

Cassol F, Portal L, Richelme S, Dupont M, Boursier Y, Arechederra M, Auphan-Anezin N, Chasson L, Lap..., Tracking Dynamics of Spontaneous Tumors in Mice Using Photon-Counting Computed Tomography., iScience 2019 Nov; 21(): 68-83.

Goossens P, Rodriguez-Vita J, Etzerodt A, Masse M, Rastoin O, Gouirand V, Ulas T, Papantonopoulou O,..., Membrane Cholesterol Efflux Drives Tumor-Associated Macrophage Reprogramming and Tumor Progression., Cell Metab 2019 Jun; 29(6): 1376-1389.e4.

Gregory Verdeil, Toby Lawrence, Anne-Marie Schmitt-Verhulst, Nathalie Auphan-Anezin, Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve Immunotherapy, <i>Contemporary Southeast Asia</i>, 2019, 11 (12), <a target="_blank" href="https://dx.doi.org/10.3390/cancers11121832">⟨10.3390/cancers11121832⟩</a>.

Anders Etzerodt, Kyriaki Tsalkitzi, Maciej Maniecki, William Damsky, Marcello Delfini, Elodie Baudoi..., Specific targeting of CD163(+) TAMs mobilizes inflammatory monocytes and promotes T cell-mediated tumor regression, <i>Journal of Experimental Medicine</i>, 2019, 216 (10), pp.2394-2411. <a target="_blank" href="https://dx.doi.org/10.1084/jem.20182124">⟨10.1084/jem.20182124⟩</a>.

Chao T, Liu Z, Zhang Y, Zhang L, Huang R, He L, Gu Y, Chen Z, Zheng Q, Shi L, Zheng W, Qi X, Kong E,..., Precise and Rapid Validation of Candidate Gene by Allele Specific Knockout With CRISPR/Cas9 in Wild Mice., Front Genet 2019 ; 10(): 124.

Ghislat G, Lawrence T, Autophagy in dendritic cells., Cell Mol Immunol 2018 Nov; 15(11): 944-952.

Villeneuve DL, Landesmann B, Allavena P, Ashley N, Bal-Price A, Corsini E, Halappanavar S, Hussell T..., Representing the Process of Inflammation as Key Events in Adverse Outcome Pathways., Toxicol Sci 2018 Jun; 163(2): 346-352.

Verzella D, Bennett J, Fischietti M, Thotakura AK, Recordati C, Pasqualini F, Capece D, Vecchiotti D..., GADD45β Loss Ablates Innate Immunosuppression in Cancer., Cancer Res 2018 Mar; 78(5): 1275-1292.

Habbeddine M, Verthuy C, Rastoin O, Chasson L, Bebien M, Bajenoff M, Adriouch S, den Haan JMM, Penni..., Receptor Activator of NF-κB Orchestrates Activation of Antiviral Memory CD8 T Cells in the Spleen Marginal Zone., Cell Rep 2017 Nov; 21(9): 2515-2527.

Cortés M, Sanchez-Moral L, de Barrios O, Fernández-Aceñero MJ, Martínez-Campanario MC, Esteve-Co..., Tumor-associated macrophages (TAMs) depend on ZEB1 for their cancer-promoting roles., EMBO J 2017 Nov; 36(22): 3336-3355.

Lee CY, Lai TY, Tsai MK, Chang YC, Ho YH, Yu IS, Yeh TW, Chou CC, Lin YS, Lawrence T, Hsu LC, The ubiquitin ligase ZNRF1 promotes caveolin-1 ubiquitination and degradation to modulate inflammation., Nat Commun 2017 Jun; 8(): 15502.

Etzerodt A, Berg RM, Plovsing RR, Andersen MN, Bebien M, Habbeddine M, Lawrence T, Møller HJ, Moest..., Soluble ectodomain CD163 and extracellular vesicle-associated CD163 are two differently regulated forms of ‘soluble CD163’ in plasma., Sci Rep 2017 Jan; 7(): 40286.

van der Vorst EPC, Theodorou K, Wu Y, Hoeksema MA, Goossens P, Bursill CA, Aliyev T, Huitema LFA, Ta..., High-Density Lipoproteins Exert Pro-inflammatory Effects on Macrophages via Passive Cholesterol Depletion and PKC-NF-κB/STAT1-IRF1 Signaling., Cell Metab 2017 Jan; 25(1): 197-207.

Lawrence T, Coordinated Regulation of Signaling Pathways during Macrophage Activation., Microbiol Spectr 2016 Oct; 4(5): .

Fan R, Toubal A, Goñi S, Drareni K, Huang Z, Alzaid F, Ballaire R, Ancel P, Liang N, Damdimopoulos ..., Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes., Nat Med 2016 Jul; 22(7): 780-91.

Pathricia V. Tilstam, Wendy Theelen, Setareh Alampour-Sarabi, Lukas Pawig, Yaw Asare, Yvonne Doering..., NON-ACTIVATABLE MUTANT OF INHIBITOR OF KAPPA B KINASE alpha (IKK alpha) EXERTS SITE-SPECIFIC EFFECTS ON ATHEROSCLEROSIS, <i>Nephrology Dialysis Transplantation</i>, 2016, 31 (1), pp.48.

Kuijpers MJ, Mattheij NJ, Cipolla L, van Geffen JP, Lawrence T, Donners MM, Boon L, Lievens D, Torti..., Platelet CD40L Modulates Thrombus Growth Via Phosphatidylinositol 3-Kinase β, and Not Via CD40 and IκB Kinase α., Arterioscler Thromb Vasc Biol 2015 Jun; 35(6): 1374-81.

Baratin M, Foray C, Demaria O, Habbeddine M, Pollet E, Maurizio J, Verthuy C, Davanture S, Azukizawa..., Homeostatic NF-κB Signaling in Steady-State Migratory Dendritic Cells Regulates Immune Homeostasis and Tolerance., Immunity 2015 Apr; 42(4): 627-39.

Zhang J, Clark K, Lawrence T, Peggie MW, Cohen P, An unexpected twist to the activation of IKKβ: TAK1 primes IKKβ for activation by autophosphorylation., Biochem J 2014 Aug; 461(3): 531-7.

Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, Gordon S, Hamilton JA, Ivashkiv LB, ..., Macrophage activation and polarization: nomenclature and experimental guidelines., Immunity 2014 Jul; 41(1): 14-20.

Dalod M, Chelbi R, Malissen B, Lawrence T, Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming., EMBO J 2014 May; 33(10): 1104-16.

Tilstam PV, Gijbels MJ, Habbeddine M, Cudejko C, Asare Y, Theelen W, Zhou B, Döring Y, Drechsler M,..., Bone marrow-specific knock-in of a non-activatable Ikkα kinase mutant influences haematopoiesis but not atherosclerosis in Apoe-deficient mice., PLoS One 2014 ; 9(2): e87452.

Mancino A, Habbeddine M, Johnson E, Luron L, Bebien M, Memet S, Fong C, Bajenoff M, Wu X, Karin M, C..., I kappa B kinase alpha (IKKα) activity is required for functional maturation of dendritic cells and acquired immunity to infection., EMBO J 2013 Mar; 32(6): 816-28.

Rastrick JM, Stevenson CS, Eltom S, Grace M, Davies M, Kilty I, Evans SM, Pasparakis M, Catley MC, L..., Cigarette smoke induced airway inflammation is independent of NF-κB signalling., PLoS One 2013 ; 8(1): e54128.

Lawrence T, Natoli G, Transcriptional regulation of macrophage polarization: enabling diversity with identity., Nat Rev Immunol 2011 Oct; 11(11): 750-61.

Lawrence T, Macrophages and NF-κB in cancer., Curr Top Microbiol Immunol 2011 ; 349(): 171-84.

Lawrence T, Fong C, The resolution of inflammation: anti-inflammatory roles for NF-kappaB., Int J Biochem Cell Biol 2010 Apr; 42(4): 519-23.

Mancino A, Lawrence T, Nuclear factor-kappaB and tumor-associated macrophages., Clin Cancer Res 2010 Feb; 16(3): 784-9.

Rodriguez-Vita J, Lawrence T, The resolution of inflammation and cancer., Cytokine Growth Factor Rev 2010 Feb; 21(1): 61-5.

Lawrence T, The nuclear factor NF-kappaB pathway in inflammation., Cold Spring Harb Perspect Biol 2009 Dec; 1(6): a001651.

Charles KA, Kulbe H, Soper R, Escorcio-Correia M, Lawrence T, Schultheis A, Chakravarty P, Thompson ..., The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans., J Clin Invest 2009 Oct; 119(10): 3011-23.

Hagemann T, Biswas SK, Lawrence T, Sica A, Lewis CE, Regulation of macrophage function in tumors: the multifaceted role of NF-kappaB., Blood 2009 Apr; 113(14): 3139-46.

Hagemann T, Lawrence T, Investigating macrophage and malignant cell interactions in vitro., Methods Mol Biol 2009 ; 512(): 325-32.

Kim C, Sano Y, Todorova K, Carlson BA, Arpa L, Celada A, Lawrence T, Otsu K, Brissette JL, Arthur JS..., The kinase p38 alpha serves cell type-specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression., Nat Immunol 2008 Sep; 9(9): 1019-27.

Hagemann T, Lawrence T, McNeish I, Charles KA, Kulbe H, Thompson RG, Robinson SC, Balkwill FR, “Re-educating” tumor-associated macrophages by targeting NF-kappaB., J Exp Med 2008 Jun; 205(6): 1261-8.

Fong CH, Bebien M, Didierlaurent A, Nebauer R, Hussell T, Broide D, Karin M, Lawrence T, An antiinflammatory role for IKKbeta through the inhibition of “classical” macrophage activation., J Exp Med 2008 Jun; 205(6): 1269-76.

Rajakariar R, Lawrence T, Bystrom J, Hilliard M, Colville-Nash P, Bellingan G, Fitzgerald D, Yaqoob ..., Novel biphasic role for lymphocytes revealed during resolving inflammation., Blood 2008 Apr; 111(8): 4184-92.

Didierlaurent A, Goulding J, Patel S, Snelgrove R, Low L, Bebien M, Lawrence T, van Rijt LS, Lambrec..., Sustained desensitization to bacterial Toll-like receptor ligands after resolution of respiratory influenza infection., J Exp Med 2008 Feb; 205(2): 323-9.

Rajakariar R, Hilliard M, Lawrence T, Trivedi S, Colville-Nash P, Bellingan G, Fitzgerald D, Yaqoob ..., Hematopoietic prostaglandin D2 synthase controls the onset and resolution of acute inflammation through PGD2 and 15-deoxyDelta12 14 PGJ2., Proc Natl Acad Sci U S A 2007 Dec; 104(52): 20979-84.

Hagemann T, Balkwill F, Lawrence T, Inflammation and cancer: a double-edged sword., Cancer Cell 2007 Oct; 12(4): 300-1.

Lawrence T, Hageman T, Balkwill F, Cancer. Sex, cytokines, and cancer., Science 2007 Jul; 317(5834): 51-2.

Fleetwood AJ, Lawrence T, Hamilton JA, Cook AD, Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: implications for CSF blockade in inflammation., J Immunol 2007 Apr; 178(8): 5245-52.

Lawrence T, Inflammation and cancer: a failure of resolution?, Trends Pharmacol Sci 2007 Apr; 28(4): 162-5.

Lawrence T, Gilroy DW, Chronic inflammation: a failure of resolution?, Int J Exp Pathol 2007 Apr; 88(2): 85-94.

Abraham SM, Lawrence T, Kleiman A, Warden P, Medghalchi M, Tuckermann J, Saklatvala J, Clark AR, Antiinflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1., J Exp Med 2006 Aug; 203(8): 1883-9.

Karin M, Lawrence T, Nizet V, Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer., Cell 2006 Feb; 124(4): 823-35.

Broide DH, Lawrence T, Doherty T, Cho JY, Miller M, McElwain K, McElwain S, Karin M, Allergen-induced peribronchial fibrosis and mucus production mediated by IkappaB kinase beta-dependent genes in airway epithelium., Proc Natl Acad Sci U S A 2005 Dec; 102(49): 17723-8.

Ruocco MG, Maeda S, Park JM, Lawrence T, Hsu LC, Cao Y, Schett G, Wagner EF, Karin M, I{kappa}B kinase (IKK){beta}, but not IKK{alpha}, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss., J Exp Med 2005 May; 201(10): 1677-87.

Lawrence T, Bebien M, Liu GY, Nizet V, Karin M, IKKalpha limits macrophage NF-kappaB activation and contributes to the resolution of inflammation., Nature 2005 Apr; 434(7037): 1138-43.

Liu GY, Doran KS, Lawrence T, Turkson N, Puliti M, Tissi L, Nizet V, Sword and shield: linked group B streptococcal beta-hemolysin/cytolysin and carotenoid pigment function to subvert host phagocyte defense., Proc Natl Acad Sci U S A 2004 Oct; 101(40): 14491-6.

Blackwell NM, Sembi P, Newson JS, Lawrence T, Gilroy DW, Kabouridis PS, Reduced infiltration and increased apoptosis of leukocytes at sites of inflammation by systemic administration of a membrane-permeable IkappaBalpha repressor., Arthritis Rheum 2004 Aug; 50(8): 2675-84.

Gilroy DW, Lawrence T, Perretti M, Rossi AG, Inflammatory resolution: new opportunities for drug discovery., Nat Rev Drug Discov 2004 May; 3(5): 401-16.

Gilroy DW, Colville-Nash PR, McMaster S, Sawatzky DA, Willoughby DA, Lawrence T, Inducible cyclooxygenase-derived 15-deoxy(Delta)12-14PGJ2 brings about acute inflammatory resolution in rat pleurisy by inducing neutrophil and macrophage apoptosis., FASEB J 2003 Dec; 17(15): 2269-71.

Colville-Nash P, Lawrence T, Air-pouch models of inflammation and modifications for the study of granuloma-mediated cartilage degradation., Methods Mol Biol 2003 ; 225(): 181-9.

Lawrence T, Willoughby DA, Gilroy DW, Anti-inflammatory lipid mediators and insights into the resolution of inflammation., Nat Rev Immunol 2002 Oct; 2(10): 787-95.

Kabouridis PS, Hasan M, Newson J, Gilroy DW, Lawrence T, Inhibition of NF-kappa B activity by a membrane-transducing mutant of I kappa B alpha., J Immunol 2002 Sep; 169(5): 2587-93.