PI: Frédéric Blanchard (DR Inserm), Benoit Le Goff (PU-PH, rheumatologist)

Jean-Marie Berthelot (PH, rheumatologist)

PhD students: Christelle Darrieutort
                          Aurélie Najm

Master 2 students: Pauline Preuss
                                   François-Marie Masson

Monocytes / macrophages play a key role in chronic inflammatory diseases. The repeated activation and alteration of their phenotype are involved in amplification and chronicity of the disease. Classically activated macrophages (M1) are pro-inflammatory phagocytes which also present antigens (in the context of MHCII) and initiate immune responses, whereas alternatively activated macrophages (M2) have immunoregulatory properties and are involved in angiogenesis, tissue repair and cancer development. Our projects focus on the cellular communications between macrophages and stromal cells (fibroblasts, osteoblasts, bone sarcoma cells) during bone inflammation. Three main projects are ongoing:

  • Project 1: Role and mechanism of action of novel anti-inflammatory cytokines from the IL-1 family in inflammatory arthritis.
Read the Research Highlight in Nature Reviews Rheumatology.
  • Project 2: Study of the synovial membrane in rheumatoid arthritis. Diagnostic and prognostic interest, and novel targeted therapies.
Read the article in Nature Reviews Rheumatology.
  • Project 3: Pathogenesis and inflammation of calcifying tendinopathy.
Supported by the Hospital Clinical Research Program CALCECHO (ClinicalTrials.gov Identifier: NCT02403856).
Read the article in Joint Bone Spine.

Fundings

PHRC

Major recent publications:

  • Najm A, le Goff B, Venet G, Garraud T, Amiaud J, Biha N, Charrier C, Touchais S, Crenn V, Blanchard F, Krenn V. IMSYC immunologic synovitis score: A new score for synovial membrane characterization in inflammatory and non-inflammatory arthritis. Joint Bone Spine. 2018 doi: 10.1016/j.jbspin.2018.04.004.
  • Garraud T, Harel M, Boutet MA, Le Goff B, Blanchard F. The enigmatic role of IL-38 in inflammatory diseases. Cytokine Growth Factor Rev. 39: 26-35, 2018.
  • Darrieutort-Laffite C, Blanchard F, Le Goff B. Calcific tendonitis of the rotator cuff: From formation to resorption. Joint Bone Spine. 85:687-692, 2018.
  • Boutet MA, Najm A, Bart G, Touchais S, Trichet V, Layrolle P, Gabay C, Palmer G, Blanchard F, Le Goff B. IL-38 overexpression induces anti-inflammatory effects in mice arthritis models and in human macrophages in vitro. Ann Rheum Dis, 76:1304-1312, 2017.
  • Boutet MA, Bart G, Gahier M, Amiaud J, Brulin B, Charrier C, Morel F, Lecron JC, Rolli-Derkinderen M, Bourreille A, Vigne S, Gabay C, Palmer G, Le Goff B, Blanchard F. Distinct Expression of IL-36a, b, g, their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn's disease. Clin Exp Immunol, 184:159-73, 2016.
  • Flanagan-Steet H, Aarnio M, Kwan B, Guihard P, Petrey A, Sahu S, Haskins M, Blanchard F, Steet R. Cathepsin-Mediated Alterations In TGFß-Related Signaling Underlie Disrupted Cartilage and Bone Maturation Associated With Impaired Lysosomal Targeting. J Bone Miner Res, 31:535-48, 2016.
  • Bougault C, Briolay A, Boutet MA, Pilet P, Delplace S, Le Goff B, Guicheux J, Blanchard F, Magne D. Wnt5a is expressed in spondyloarthritis and exerts opposite effects on enthesis and bone in murine organ and cell cultures. Transl Research, 166:627-38, 2015.
  • Rabeony H, Vasseur P, Pohin M, Petit-Paris I, Jégou JF, Favot L, Frouin E, Boutet MA, Blanchard F, Togbe D, Ryffel B, Bernard FX, Lecron JC, Morel F. IMQ-induced skin inflammation in mice is dependent on IL-1R1 and MyD88 signaling but independent of the NLRP3 inflammasome. Eur J Immunol, 45:2847-57, 2015.
  • Guihard P, Boutet MA, Brounais-Le Royer B, Gamblin AL, Amiaud J, Renaud A, Berreur M, Rédini F, Heymann D, Layrolle P, Blanchard F. Oncostatin M, an inflammatory cytokine produced by macrophages, supports intramembranous bone healing in a mouse model of tibia injury. Am J Pathol, 185:765-75, 2015.
  • Monderer D, Luseau A, Bellec A, David E, Ponsolle S, Saiagh S, Bercegeay S, Piloquet P, Denis MG, Lodé L, Rédini F, Biger M, Heymann D, Heymann MF, Le Bot R, Gouin F, Blanchard F. New chondrosarcoma cell lines and mouse models to study the link between chondrogenesis and chemoresistance. Lab Invest. 93:1100-14, 2013.
  • David E, Tirode F, Baud'huin M, Guihard P, Laud K, Delattre O, Heymann MF, Heymann D, Redini F, Blanchard F. Oncostatin M is a growth factor for Ewing sarcoma. Am J Pathol. 181:1782-95, 2012.
  • Guihard P, Danger Y, Brounais B, David E, Brion R, Delecrin J, Richards CD, Chevalier S, Rédini F, Heymann D, Gascan H, Blanchard F. Induction of osteogenesis in mesenchymal stem cells by activated monocytes / macrophages depends on Oncostatin M signaling. Stem Cells. 30:762-72, 2012.
  • Chemel M, Le Goff B, Brion R, Cozic C, Berreur M, Amiaud J, Bougras G, Touchais S, Blanchard F, Heymann MF, Berthelot JM, Verrecchia F, Heymann D. Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients. Ann Rheum Dis. 71:150-4, 2012.