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.