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Régulations des réponses cellulaires immunitaires par les mastocytes au cours des rejets d'allogreffe de peau d'oreille chez la souris

Abstract : Skin allografts are performed after injuries, burns or other skin diseases in order to restore skin protection. The real challenge is to induce a better transplant tolerance by decreasing or preventing immunosuppressive treatments which trigger side effects. Mast cells (MC) are part of complex cellular networks in every mucosal and connective tissues such as the skin and are playing key regulatory roles for initiating local inflammatory responses. Using our new Red Mast cell and Basophil (RMB) mouse model that allows visualization and conditional depletion of MC by diphteria toxin injection, we showed that both graft and host MC accelerate rejection in a sex mismatch ear skin graft model. Graft rejection is speeded up in the presence of mast cells (t1/2 3 versus 6 days). A strong recruitment of inflammatory cells, especially neutrophils, were strongly recruited both on the graft site and in the draining lymph node at 2 and 6 days post graft compared to the control condition ie sexmatch female-female ear skin graft. No marked MC-dependent differences were seen in T cell or monocyte/macrophage infiltration, while B cells showed a late increase in skin allografts in the absence of MCs. Inflammatory cytokines such as KC, MIP-2 and TNF were clearly upregulated supporting the early neutrophil infiltration to mediate graft rejection. We next blocked MC activation using cromolyn treatment, a MC stabilizer and observed same delay in the graft rejection confirming the MC rule. Treatments with ketotifen, a histamine type I receptor antagonist, or using mcpt4 chymase deficient mice showed a light delay of the graft rejection. Depletion of neutrophils with a specific antibody (NIMP) confirmed their involvement in skin rejection. Together our data indicate that mast cells after degranulation promote the recruitment of inflammatory cells, such as neutrophils, which contribute to the acceleration of an ear skin graft rejection.
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Submitted on : Wednesday, March 3, 2021 - 2:18:08 PM
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Flavie Ngo Nyekel. Régulations des réponses cellulaires immunitaires par les mastocytes au cours des rejets d'allogreffe de peau d'oreille chez la souris. Médecine humaine et pathologie. Université Sorbonne Paris Cité, 2018. Français. ⟨NNT : 2018USPCC291⟩. ⟨tel-03157824⟩

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