| RRC ID |
84424
|
| Author |
Yoshikawa T, Minaga K, Hara A, Sekai I, Kurimoto M, Masuta Y, Otsuka Y, Takada R, Kamata K, Park AM, Takamura S, Kudo M, Watanabe T.
|
| Title |
Disruption of the intestinal barrier exacerbates experimental autoimmune pancreatitis by promoting the translocation of Staphylococcus sciuri into the pancreas.
|
| Journal |
Int Immunol
|
| Abstract |
Autoimmune pancreatitis (AIP) and IgG4-related disease (IgG4-RD) are new disease entities characterized by enhanced IgG4 antibody responses and involvement of multiple organs, including the pancreas and salivary glands. Although the immunopathogenesis of AIP and IgG4-RD is poorly understood, we previously reported that intestinal dysbiosis mediates experimental AIP through the activation of IFN-α- and IL-33-producing plasmacytoid dendritic cells (pDCs). Because intestinal dysbiosis is linked to intestinal barrier dysfunction, we explored whether the latter affects the development of AIP and autoimmune sialadenitis in MRL/MpJ mice treated with repeated injections of polyinosinic-polycytidylic acid [poly (I:C)]. Epithelial barrier disruption was induced by the administration of dextran sodium sulfate (DSS) in the drinking water. Mice co-treated with poly (I:C) and DSS, but not those treated with either agent alone, developed severe AIP, but not autoimmune sialadenitis, which was accompanied by the increased accumulation of IFN-α- and IL-33-producing pDCs. Sequencing of 16S ribosomal RNA revealed that Staphylococcus sciuri translocation from the gut to the pancreas was preferentially observed in mice with severe AIP co-treated with DSS and poly (I:C). The degree of experimental AIP, but not of autoimmune sialadenitis, was greater in germ-free mice mono-colonized with S. sciuri and treated with poly (I:C) than in germ-free mice treated with poly (I:C) alone, which was accompanied by the increased accumulation of IFN-α- and IL-33-producing pDCs. Taken together, these data suggest that intestinal barrier dysfunction exacerbates AIP through the activation of pDCs and translocation of S. sciuri into the pancreas.
|
| Volume |
34(12)
|
| Pages |
621-634
|
| Published |
2022-12-31
|
| DOI |
10.1093/intimm/dxac039
|
| PII |
6677576
|
| PMID |
36044992
|
| MeSH |
Animals
Autoimmune Diseases*
Autoimmune Pancreatitis*
Dysbiosis
Immunoglobulin G4-Related Disease*
Interferon-alpha
Interleukin-33
Mice
Mice, Inbred Strains
Pancreas / pathology
Pancreatitis* / chemically induced
Pancreatitis* / pathology
Poly I-C
Sialadenitis* / pathology
|
| IF |
3.519
|
| Resource |
| General Microbes |
JCM 2425 |
