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Acute small intestinal inflammation results in persistent lymphatic alterations.
- Source :
-
American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2018 Mar 01; Vol. 314 (3), pp. G408-G417. Date of Electronic Publication: 2017 Dec 14. - Publication Year :
- 2018
-
Abstract
- Inflammatory bowel disease (IBD) has a complex pathophysiology with limited treatments. Structural and functional changes in the intestinal lymphatic system have been associated with the disease, with increased risk of IBD occurrence linked to a history of acute intestinal injury. To examine the potential role of the lymphatic system in inflammation recurrence, we evaluated morphological and functional changes in mouse mucosal and mesenteric lymphatic vessels, and within the mesenteric lymph nodes during acute ileitis caused by a 7-day treatment with dextran sodium sulfate (DSS). We monitored whether the changes persisted during a 14-day recovery period and determined their potential consequences on dendritic cell (DC) trafficking between the mucosa and lymphoid tissues. DSS administration was associated with marked lymphatic abnormalities and dysfunctions exemplified by lymphangiectasia and lymphangiogenesis in the ileal mucosa and mesentery, increased mesenteric lymphatic vessel leakage, and lymphadenopathy. Lymphangiogenesis and lymphadenopathy were still evident after recovery from intestinal inflammation and correlated with higher numbers of DCs in mucosal and lymphatic tissues. Specifically, a deficit in CD103 <superscript>+</superscript> DCs observed during acute DSS in the lamina propria was reversed and further enhanced during recovery. We concluded that an acute intestinal insult caused alterations of the mesenteric lymphatic system, including lymphangiogenesis, which persisted after resolution of inflammation. These morphological and functional changes could compromise DC function and movement, increasing susceptibility to further gastrointestinal disease. Elucidation of the changes in mesenteric and intestinal lymphatic function should offer key insights for new therapeutic strategies in gastrointestinal disorders such as IBD. NEW & NOTEWORTHY Lymphatic integrity plays a critical role in small intestinal homeostasis. Acute intestinal insult in a mouse model of acute ileitis causes morphological and functional changes in mesenteric and intestinal lymphatic vessels. While some of the changes significantly regressed during inflammation resolution, others persisted, including lymphangiogenesis and altered dendritic cell function and movement, potentially increasing susceptibility to the recurrence of gastrointestinal inflammation.
- Subjects :
- Animals
Antigens, CD metabolism
Cell Movement
Dendritic Cells metabolism
Dendritic Cells pathology
Dextran Sulfate
Disease Models, Animal
Ileitis chemically induced
Ileitis metabolism
Ileum metabolism
Integrin alpha Chains metabolism
Intestinal Mucosa metabolism
Lymph Nodes metabolism
Lymphangiectasis, Intestinal chemically induced
Lymphangiectasis, Intestinal metabolism
Lymphatic Vessels metabolism
Male
Mice, Inbred C57BL
Time Factors
Ileitis pathology
Ileum pathology
Intestinal Mucosa pathology
Lymph Nodes pathology
Lymphangiectasis, Intestinal pathology
Lymphangiogenesis
Lymphatic Vessels pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1547
- Volume :
- 314
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Publication Type :
- Academic Journal
- Accession number :
- 29351397
- Full Text :
- https://doi.org/10.1152/ajpgi.00340.2017