TY - JOUR
T1 - Therapeutic faecal microbiota transplantation controls intestinal inflammation through IL10 secretion by immune cells
AU - Burrello, Claudia
AU - Garavaglia, Federica
AU - Cribiù, Fulvia Milena
AU - Ercoli, Giulia
AU - Lopez, Gianluca
AU - Troisi, Jacopo
AU - Colucci, Angelo
AU - Guglietta, Silvia
AU - Carloni, Sara
AU - Guglielmetti, Simone
AU - Taverniti, Valentina
AU - Nizzoli, Giulia
AU - Bosari, Silvano
AU - Caprioli, Flavio
AU - Rescigno, Maria
AU - Facciotti, Federica
PY - 2018/12/5
Y1 - 2018/12/5
N2 - Alteration of the gut microbiota has been associated with different gastrointestinal disorders. Normobiosis restoration by faecal microbiota transplantation (FMT) is considered a promising therapeutic approach, even if the mechanisms underlying its efficacy are at present largely unknown. Here we sought to elucidate the functional effects of therapeutic FMT administration during experimental colitis on innate and adaptive immune responses in the intestinal mucosa. We show that therapeutic FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis through the simultaneous activation of different immune-mediated pathways, ultimately leading to IL-10 production by innate and adaptive immune cells, including CD4+ T cells, iNKT cells and Antigen Presenting Cells (APC), and reduces the ability of dendritic cells, monocytes and macrophages to present MHCII-dependent bacterial antigens to colonic T cells. These results demonstrate the capability of FMT to therapeutically control intestinal experimental colitis and poses FMT as a valuable therapeutic option in immune-related pathologies.
AB - Alteration of the gut microbiota has been associated with different gastrointestinal disorders. Normobiosis restoration by faecal microbiota transplantation (FMT) is considered a promising therapeutic approach, even if the mechanisms underlying its efficacy are at present largely unknown. Here we sought to elucidate the functional effects of therapeutic FMT administration during experimental colitis on innate and adaptive immune responses in the intestinal mucosa. We show that therapeutic FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis through the simultaneous activation of different immune-mediated pathways, ultimately leading to IL-10 production by innate and adaptive immune cells, including CD4+ T cells, iNKT cells and Antigen Presenting Cells (APC), and reduces the ability of dendritic cells, monocytes and macrophages to present MHCII-dependent bacterial antigens to colonic T cells. These results demonstrate the capability of FMT to therapeutically control intestinal experimental colitis and poses FMT as a valuable therapeutic option in immune-related pathologies.
KW - Adaptive Immunity
KW - Animals
KW - Antigen-Presenting Cells/immunology
KW - CD4-Positive T-Lymphocytes/immunology
KW - Colitis/genetics
KW - Dendritic Cells/immunology
KW - Disease Models, Animal
KW - Fecal Microbiota Transplantation
KW - Female
KW - Gastrointestinal Microbiome
KW - Humans
KW - Immunity, Innate
KW - Interleukin-10/genetics
KW - Intestinal Mucosa/immunology
KW - Macrophages/immunology
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Natural Killer T-Cells/immunology
U2 - 10.1038/s41467-018-07359-8
DO - 10.1038/s41467-018-07359-8
M3 - Article
C2 - 30518790
VL - 9
SP - 5184
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
ER -