Presentation

Basophils, Mast cells and Immunopathology (BMI)
Nicolas Charles  & Ulrich Blank

Besides their well-known role in allergies, mast cells (MC) and basophils (Ba) are important orchestrators of the inflammatory process with possible beneficial and pathological consequences. The team’s project focuses on the role of mast cells and basophils in immunopathology mainly in a non-allergic context using both fundamental and clinical approaches with local clinical departments. The strategy is based on the identification of the receptors expressed on these cells, their signaling pathways and the mechanism controlling the subsequent release of inflammatory mediators and on the effect of these mediators on tissue function, particularly on kidney, in animal models and patient samples. Both approaches are tightly linked to the analysis of therapeutic/prognostic/diagnostic potential of each of these steps using in vitro and in vivo approaches. Our team is particularly focused on the study of the role of basophils in lupus nephritis and of mast cells in renal diseases and fibrosis development as well as in tissue transplantation. 

The major research axes developed in our team are the following:

(A) Study of the molecular mechanisms and effectors regulating inflammatory mediator secretion in mast cells and basophils. This includes the study of new receptors of basophil function as well as the study of early and late signaling events involved in degranulation and cytokine chemokine secretion (axes 1-3).

(B) Study of the role of mast cells and basophils in immunopathology. This includes the analysis of the role of mast cells and their interaction with other inflammatory cells in fibrosis development, acute kidney injury and transplantation. The crosstalk of basophils with other innate and adaptive immune cells in the development of autoimmune diseases (in particular systemic lupus erythematous) is studied. We also investigate the role of these two cell compartments in the amplification of lupus disease flares and severe cardiovascular outcomes in a translational approach (axes 4-6).

Selected publications
  • Ngo Nyekel F, Pacreau E, Benadda S, Msallam R, Åbrink M, Pejler G, Davoust J, Benhamou M, Charles N, Launay P, Blank U, Gautier G. Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment. Front Immunol. 2018, 9:2690.
  • Madera-Salcedo IK, Danelli L, Tiwari N, Dema B, Pacreau E, Vibhushan S, Birnbaum J, Agabriel C, Liabeuf V, Klingebiel C, Menasche G, Macias-Silva M, Benhamou M, Charles N, González-Espinosa C, Vitte J, Blank U. Tomosyn functions as a PKCδ-regulated fusion clamp in mast cell degranulation. Sci Signal. 2018, 11(537).
  • Pellefigues C, Dema B, Lamri Y, Saidoune F, Chavarot N, Lohéac C, Pacreau E, Dussiot M, Bidault C, Marquet F, Jablonski M, Chemouny JM, Jouan F, Dossier A, Chauveheid MP, Gobert D, Papo T, Karasuyama H, Sacré K, Daugas E, Charles N. Prostaglandin D2 amplifies lupus disease through basophil accumulation in lymphoid organs. Nat Commun. 2018, 9(1):725.
  • Danelli L, Madjene LC, Madera-Salcedo I, Gautier G, Pacreau E, Ben Mkaddem S, Charles N, Daugas E, Launay P, Blank U. Early Phase Mast Cell Activation Determines the Chronic Outcome of Renal Ischemia-Reperfusion Injury. J Immunol. 2017, 198(6):2374-2382.
  • Kassas-Guediri A, Coudrat J, Pacreau E, Launay P, Monteiro RC, Blank U, Charles N, Benhamou M. Phospholipid scramblase 1 amplifies anaphylactic reactions in vivo. PLoS One. 2017, 12(3):e0173815
Team members
Equipe Ulrich Blank, DR 
Nicolas Charles, DR 
Chercheurs Marc Benhamou, CR 
  Pierre Launay, DR 
  Grégory Gautier, MCF 
  Eric Daugas, PUPH
  Alaa El Ghoneimi, PUPH
  Thomas Papo, PUPH
  Karim Sacre, PHU
  Hanouna Guillaume, PH
Doctorants  John Tchen
Manuela Bratti
Yasmine Lamri
  Fany Saidoune
Post-doctorants Karla Ramirez Valadez
Ingénieurs et techniciens Emeline Lebourdais, AI
Shamila Vibhushan, AI