| RRC ID |
87942
|
| Author |
Ansary MM, Ishihara S, Oka A, Kusunoki R, Oshima N, Yuki T, Kawashima K, Maegawa H, Kashiwagi N, Kinoshita Y.
|
| Title |
Apoptotic cells ameliorate chronic intestinal inflammation by enhancing regulatory B-cell function.
|
| Journal |
Inflamm Bowel Dis
|
| Abstract |
Apoptosis is a programmed physiological death of unwanted cells, and handling of apoptotic cells (ACs) is thought to have profound effects on immune-mediated disorders. However, there is scant information regarding the role of ACs in intestinal inflammation, in which immune homeostasis is a major concern. To investigate this, we injected ACs into a severe combined immunodeficiency adoptive transfer model of chronic colitis in the presence and absence of cotransferred whole B or regulatory B cell (Breg)-depleted B cells. We also injected syngeneic ACs into AKR/N mice as a control and into milk fat globule-epidermal growth factor 8 knockout mice deficient of phagocytic function. Chronic colitis severity was significantly reduced in the AC as opposed to the phosphate-buffered saline group with cotransferred whole B cells. The AC-mediated effect was lost in the absence of B cells or presence of Breg-depleted B cells. In addition, ACs induced splenic B cells to secrete significantly increased levels of interleukin 10 in AKR/N mice but not milk fat globule-epidermal growth factor 8 knockout mice. Apoptotic leukocytes were induced by reactive oxygen species during granulocyte/monocyte apheresis therapy in rabbits and H2O2-induced apoptotic neutrophils ameliorated mice colitis. Our results indicate that ACs are protective only in the presence of B cells and phagocytosis of ACs induced interleukin 10 producing Bregs. Thus, the ameliorative effect seen in this study might have been exerted by AC-induced Bregs through increased production of the immunosuppressive cytokine interleukin 10, whereas an AC-mediated effect may contribute to the anti-inflammatory effect of granulocyte/monocyte apheresis as a novel therapeutic mechanism for inflammatory bowel disease.
|
| Volume |
20(12)
|
| Pages |
2308-20
|
| Published |
2014-12-1
|
| DOI |
10.1097/MIB.0000000000000240
|
| PMID |
25358066
|
| MeSH |
Animals
Apoptosis / immunology*
Arthritis, Experimental / immunology*
Arthritis, Experimental / metabolism
Arthritis, Experimental / pathology
B-Lymphocytes, Regulatory / immunology*
B-Lymphocytes, Regulatory / metabolism
B-Lymphocytes, Regulatory / pathology
Cells, Cultured
Chronic Disease
Colitis / immunology*
Colitis / metabolism
Colitis / pathology
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Immunoenzyme Techniques
Inflammation / immunology*
Inflammation / metabolism
Inflammation / pathology
Intestinal Mucosa / immunology*
Intestinal Mucosa / metabolism
Intestinal Mucosa / pathology
Mice
Mice, Inbred AKR
Mice, Inbred C57BL
Mice, Knockout
Mice, SCID
Neutrophils / immunology
Neutrophils / metabolism
Neutrophils / pathology
RNA, Messenger / genetics
Rabbits
Reactive Oxygen Species / metabolism
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
|
| IF |
4.261
|
| Resource |
| Mice |
RBRC01726 |
