Figure 1. Characteristics of patients with type 1 autoimmune pancreatitis.
Three patients with type 1 autoimmune pancreatitis were enrolled in this study. They were treated with prednisolone (PSL) for the induction of remission. (A) Patient age, sex, and affected organs.(B) Serum concentrations of IgG4 before and after PSL treatment. (C) Contrast-enhanced computed tomography images of case 1 before (left) and after (right) PSL treatment. (D) Fecal samples obtained from all the patients were subjected to 16S ribosomal RNA sequencing to evaluate the composition of intestinal bacteria. Alpha rarefaction plots. Species richness expressed as the number of operational taxonomic units at increasing sequencing depth is illustrated. Results are expressed as the mean + standard error.
Figure 2. Gut microbiome alterations in patients with type 1 autoimmune pancreatitis before and after prednisolone treatment.Fecal samples were subjected to 16S ribosomal RNA sequencing to evaluate the composition of intestinal bacteria. A total of six samples were obtained from three patients with type 1 autoimmune pancreatitis before and after prednisolone (PSL) treatment. Relative bacterial abundance at the order level is shown. Each bar shows relative bacterial abundance in each patient before and after PSL treatment.
Figure 3. Reduction of Enterobacteriales in patients with type 1 autoimmune pancreatitis after prednisolone treatment. A total of six samples were obtained from three patients with type 1 autoimmune pancreatitis before and after prednisolone (PSL) treatment. Fecal samples were subjected to 16S ribosomal RNA sequencing to evaluate the composition of intestinal bacteria. Alterations in gut microbiota, at the order level, are shown for each patient.
Figure 4. Reduction of Klebsiella species in patients with type 1 autoimmune pancreatitis after prednisolone treatment. A total of six samples were obtained from three patients with type 1 autoimmune pancreatitis before and after prednisolone (PSL) treatment. Fecal samples were subjected to 16S ribosomal RNA sequencing to evaluate the composition of intestinal bacteria. (A)Relative abundance of a broad range of intestinal bacteria is shown at the genus level. Results are expressed as the mean + standard error in three samples before (black bar) and after (white bar) PSL treatment. (B) Alterations in gut microbiota, at the genus level, are shown for each patient.
Figure 5. Increased sensitivity to polyinosinic-polycytidylic acid-induced experimental autoimmune pancreatitis in MRL/MpJ mice orally administered with heat-killed Klebsiella pneumoniae. MRL/MpJ mice were injected with polyinosinic-polycytidylic acid (poly (I:C), 10 µg), orally administered heat-killed K. pneumoniae , received both these treatments twice a week for a total of 16 times, or left untreated. Mice were sacrificed 3 h after the final injection of poly (I:C) or oral adiministration of heat-killed K. pneumoniae .(A) Pancreatic tissues were stained with hematoxylin and eosin (H&E). Representative H&E images of the four experimental groups are shown (magnification 400×). (B) Pathology scores as assessed by H&E staining (n = 5 for all four experimental groups). Results are expressed as the mean + standard error. *P <0.05, as compared with mice treated with poly (I:C) alone.
Figure 6. Pancreatic accumulation of plasmacytoid dendritic cells in MRL/MpJ mice that received oral administration of heat-killedKlebsiella pneumoniae and intraperitoneal injections of polyinosinic-polycytidylic acid. MRL/MpJ mice were injected with polyinosinic-polycytidylic acid (poly (I:C), 10 µg), orally administered heat-killed K. pneumoniae , received both these treatments twice a week for a total of 16 times, or left untreated. (A, B)Pancreatic mononuclear cells were analyzed by flow cytometry to evaluate the population of plasmacytoid dendritic cell antigen 1 (PDCA-1)+B220low plasmacytoid dendritic cells (pDCs), CD11b+ myeloid cells, CD11c+ DCs, CD3+ T cells, and B220+ B cells (n = 5 for all four experimental groups). Results are expressed as the mean + standard error. **P < 0.01, as compared with mice treated with poly (I:C) alone.
Figure 7. Pancreatic expression of proinflammatory cytokines in MRL/MpJ mice that received oral administration of heat-killedKlebsiella pneumoniae and intraperitoneal injections of polyinosinic-polycytidylic acid. MRL/MpJ mice were injected with polyinosinic-polycytidylic acid (poly (I:C), 10 µg), orally administered heat-killed K. pneumoniae , received both these treatments twice a week for a total of 16 times, or left untreated. Pancreatic levels of pro-inflammatory cytokines were determined by the enzyme-linked immunosorbent assay (n = 5 for all four experimental groups). Results are expressed as the mean + standard error. **P< 0.01, as compared with mice treated with poly (I:C) alone.