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Interleukin-22 : Functional analysis in zebrafish ; Interleukine-22 : Analyse fonctionnelle chez le poisson zèbre

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  • معلومة اضافية
    • Contributors:
      Génétique et Biologie du Développement; Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); Université Paris sciences et lettres; Pedro Hernandez Cerda
    • بيانات النشر:
      CCSD
    • الموضوع:
      2023
    • نبذة مختصرة :
      Cytokines promote gut defense and homeostasis. Among key gut cytokines, interleukin-22 (IL-22) is produced by immune cells and primarily targets epithelial cells. IL-22 protects the gut from pathogens by inducing anti-microbial peptides expression and promoting tissue repair. Dysregulation of this cytokine can lead to inflammatory bowel disease and cancer. During development, the post-embryonic gut is colonized by commensal microorganisms that promote maturation of the gut and its immune system. Nevertheless, whether and how cytokines such as IL-22 play a role in gut organ development and maturation during this critical time window remains unclear. The zebrafish allows us to visualize and manipulate physiological processes in vivo since early development due to its external development and transparency.During my PhD, I wanted to decipher the function of il22 in the developing gut. My data show that il22 is expressed in larval gut epithelial cells before il22-expressing lymphocytes appear in the gut. I identified enteroendocrine cells (EECs), a gut epithelial cell subtype, as the main source of il22 in larvae. Furthermore, I revealed conservation of the IL-22 signaling pathway, its transcriptional regulation by microbe sensing, and its antibacterial function in the gut. My latest data suggest that il22 expression can also be induced by the activation of Trpa1, a receptor known to recognize tryptophan metabolites in zebrafish and mice. Finally, I found a novel role of IL-22 in modulating gut motility in zebrafish. Mechanistically, dysbiosis was observed in il22-/-, along with potential defects in the production of bacteria-derived metabolites in the gut. Surprisingly, we found that the microbiota from wild-type larvae was able to restore the gut motility impairment of il22-/-, highlighting the important role of the microbiota in il22-mediated regulation of this process. Furthermore, an impairment was found in EECs function, which are known to be sensitive and respond to microbial cues. The dysregulation of EECs ...
    • Relation:
      NNT: 2023UPSLS061
    • الدخول الالكتروني :
      https://theses.hal.science/tel-04842194
      https://theses.hal.science/tel-04842194v1/document
      https://theses.hal.science/tel-04842194v1/file/Curie_RABAHI_2023_archivage.pdf
    • Rights:
      info:eu-repo/semantics/OpenAccess
    • الرقم المعرف:
      edsbas.4F82903F