INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Human Intestinal Transplant: is IL-22 stimulation of Intestinal Stem Cells a new partner for immunosuppressive therapies?
Autor/es:
MARÍA VIRGINIA GENTILINI; CAROLINA RUMBO; MARTIN RUMBO; MELISA PUCCI MOLINERIS; VIRGINIA GONZÁLEZ POLO; DOMINIK MEIER; ALBANIS PARADA MONCADA; HECTOR SOLAR MUÑIZ; GABRIEL GONDOLESI
Lugar:
Paris
Reunión:
Congreso; XVI International Congress of Intestinal rehabilitation and Transplant association; 2019
Resumen:
Acute cellular rejection (ACR) is leading cause of graft loss and death in intestinaltransplant (ITx) patients. ACR promotes intestinal injury, disruption of the mucosalbarrier, organ dysfunction and bacterial translocation. Epithelial regeneration is criticalto reverse the situation. The intestinal stem cell (ISC) provides signals supportingnormal epithelial maintenance. It has been shown that innate lymphoid cells 3 (ILC3),potent producers of IL-22 after intestinal injury, increase proliferation and expansion ofthe ISC in an IL-22-dependent fashion. Therefore, we aimed to evaluate theimmunological status during the ACR focusing on the axis ILC3/IL-22/IL22R/ISC. Todo this, lamina propria cells of biopsies were isolated from ITx [Non-rejection(NR)=17; Mild rejection (MR)=4] and non-transplant patients (NITx)=7. Enrichment ofILCs and CD4 population was done using MACS technology. ILC3 were determinedby flow cytometry. CD4 T cells were isolated and the expression levels of functionalmarkers of Th1 (Tbet, IFN-γ), Th2 (GATA3, IL-13), Th22/17 (RORC, IL-22, IL-17A),Tregs (Foxp3, TGF-β) were evaluated by qPCR. Total levels of IL-22 in biopsies[NR=5 and Moderate rejection (MoR)=6] were measured by qPCR. ISC IL-22R+ weredetected by immunohistochemical staining [NR=13; MR=9, MoR=12, Severe rejection(SR)=5]. The results showed that during ACR the expression of Tbet, GATA3, RORC,Foxp3 were significantly decreased (P=0.05). Although the total percentage of ILC3swas not impaired (P=0.47); a reduction of ILC3 NCR+/NCR- ratio was observed. ISCIL-22R+ number was similar in all groups studied (P=0.21) while IL-22R expressionshowed a trend to be increased (P=0.06). Levels of IL-22 in ITxMoR were lower thanin NRITx patients with normal biopsies (P=0.063) and NITx biopsies. In conclusion,during rejection CD4 population (TH1, TH2, TH17/22, Tregs) and ILC3/IL-22/IL-22Raxis are affected. In this context ISC number not only is unaffected, but also is able toincrease IL-22R expression. Finally, the variation in the ILC3 NCR+/NCR- ratioobserved during ACR could explained, in part, the impairment in the epithelialregeneration observed during this process. Thus, our findings reveal that IL-22 canpotentially be uses as a new therapeutic approach to be used in conjunction withimmunosuppressants in order to promote mucosal regeneration. Due to the smallnumber of patients evaluated, this preliminary study is currently being extended with alarger population.