PATHOGEN-SPECIFIC T CELLS FROM PATIENTS WITH INFLAMMATORY BOWEL DISEASES CAN BE MODULATED BY PROBIOTICS FROM KEFIR

RENATA CURCIARELLO; SANTIAGO BRAYER; GUILLERMO, DOCENA; AUGUSTO VILLAVERDE; FRANCISCO TUFARÉ; LAURA GARBI; GUSTAVO J. CORREA; MARTÍN YANTORNO; ALICIA SAMBUELLI; ANDRÉS ROCCA; CANZIANI KARINA; CECILIA ALVAREZ; AYELÉN HUGO; MARTÍN RUMBO; AGUSTINA ERREA; SERRADELL MARÍA DE LOS ANGELES; EMMANUEL BARBIERA; ILEANA SALTO; MUGLIA CECILIA

Mar del Plata

Congreso; SAIC SAI SAFIS 2018; 2018

Kefir is a fermented milk withhealth-promoting properties. Lamina propria T cells (LPTC) play a central role inthe pathogenesis of Inflammatory Bowel Diseases (IBD). These cells contribute tomucosal inflammation by secreting pro-inflammatory cytokines and beingresistant to apoptosis. We aimed to modulate the proliferation and thepro-inflammatory response of pathogen-specific LPTC from IBD patients usingmicroorganisms from kefir.Colonic biopsies from IBDpatients were incubated with probiotics from kefir and cytokines insupernatants were evaluated by ELISA afterwards. LPTC were isolated from biopsies(N=23; 7 from Crohn's Disease patients-CD. and 15 from ulcerative colitis-UCpatients) by collagenolytic digestion. In order to expand pathogen-specific Tlymphocytes, cells were cultured with enteroadhesive (EA) Escherichiacoli extract and IL-2 for 10 days. Thereafter, LPTC were incubatedwith anti-CD3/anti-CD28 and with microorganisms from kefir (Enterococcus duransand Lactobacillus kefiri), their conditioned media or 10 µM lactate for 48hs.  LPTCs proliferation (CFSE) and TNF-α,IFN-γ, IL-6, IL-10 and IL-13 cytokine secretion were evaluated (ELISA).Wefound that E. durans and L. kefiri diminished thepro-inflammatory cytokine production by inflamed tissues (IL-6: 1800±670and  576±3 vs 6900±2000 pg/ml basalproduction, respectively; IL-8: 38000±11000 and  32000±7300 vs 80000±27000 pg/ml basalproduction, respectively). EA E. coli specific LPTC lines weredeveloped from all patients. Cellular proliferation of activated CD4+/CFSE-/PI-LPTC decreased significantly with L. kefiri , E. durans and lactate (P<0.01, N=15),but not with conditioned media. Moreover, TNF-α (P<0.05, N=10), IFN-γ (P<0.05,N=11) and IL-6 (P<0.05, N=8) secretion decreased with the presence ofprobiotics, their supernatants or lactate. No significant differences were observedfor IL-10 and IL-13. Our results showed thatprobiotic strains from kefir and their metabolites modulated pathogen-specificactivated T cells from IBD patients. These results could contribute to futuretherapeutic approaches for IBD.