Mechanisms of lymphoid depletion in bowel obstruction
Background and aims: Bowel obstruction (BO) causes not only gastrointestinal dysfunctions but also systemic responses such as sepsis, infections, and immune impairments. The mechanisms involved are not well understood. In this study, we tested the hypothesis that BO leads to lymphoid depletion in pr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.1005088/full |
| _version_ | 1811272449047658496 |
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| author | You-Min Lin You-Min Lin Shrilakshmi Hegde Yingzi Cong Xuan-Zheng Shi |
| author_facet | You-Min Lin You-Min Lin Shrilakshmi Hegde Yingzi Cong Xuan-Zheng Shi |
| author_sort | You-Min Lin |
| collection | DOAJ |
| description | Background and aims: Bowel obstruction (BO) causes not only gastrointestinal dysfunctions but also systemic responses such as sepsis, infections, and immune impairments. The mechanisms involved are not well understood. In this study, we tested the hypothesis that BO leads to lymphoid depletion in primary and peripheral lymphoid organs, which may contribute to systemic responses. We also sought to uncover mechanisms of lymphoid depletion in BO.Methods: Partial colon obstruction was induced with a band in the distal colon of Sprague-Dawley rats, and wild-type and osteopontin knockout (OPN−/−) mice. Obstruction was maintained for 7 days in rats and 4 days in mice. Thymus, bone marrow, spleen, and mesenteric lymph node (MLN) were taken for flow cytometry analysis.Results: The weight of thymus, spleen, and MLN was significantly decreased in BO rats, compared to sham. B and T lymphopoiesis in the bone marrow and thymus was suppressed, and numbers of lymphocytes, CD4+, and CD8+ T cells in the spleen and MLN were all decreased in BO. Depletion of gut microbiota blocked BO-associated lymphopenia in the MLN. Corticosterone antagonism partially attenuated BO-associated reduction of lymphocytes in the thymus and bone marrow. Plasma OPN levels and OPN expression in the distended colon were increased in BO. Deletion of the OPN gene did not affect splenic lymphopenia, but attenuated suppression of lymphopoiesis in the bone marrow and thymus in BO.Conclusions: BO suppresses lymphocyte generation and maintenance in lymphoid organs. Mechanical distention-induced OPN, corticosterone, and gut microbiota are involved in the immune phenotype in BO. |
| first_indexed | 2024-04-12T22:40:26Z |
| format | Article |
| id | doaj.art-5f0e3fcdc3994e3db0e93edf9c8d04c4 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-12T22:40:26Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-5f0e3fcdc3994e3db0e93edf9c8d04c42022-12-22T03:13:45ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-09-011310.3389/fphys.2022.10050881005088Mechanisms of lymphoid depletion in bowel obstructionYou-Min Lin0You-Min Lin1Shrilakshmi Hegde2Yingzi Cong3Xuan-Zheng Shi4Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, United StatesDepartment of Pathology, University of Texas Medical Branch, Galveston, TX, United StatesDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, TX, United StatesDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, United StatesDepartment of Internal Medicine, University of Texas Medical Branch, Galveston, TX, United StatesBackground and aims: Bowel obstruction (BO) causes not only gastrointestinal dysfunctions but also systemic responses such as sepsis, infections, and immune impairments. The mechanisms involved are not well understood. In this study, we tested the hypothesis that BO leads to lymphoid depletion in primary and peripheral lymphoid organs, which may contribute to systemic responses. We also sought to uncover mechanisms of lymphoid depletion in BO.Methods: Partial colon obstruction was induced with a band in the distal colon of Sprague-Dawley rats, and wild-type and osteopontin knockout (OPN−/−) mice. Obstruction was maintained for 7 days in rats and 4 days in mice. Thymus, bone marrow, spleen, and mesenteric lymph node (MLN) were taken for flow cytometry analysis.Results: The weight of thymus, spleen, and MLN was significantly decreased in BO rats, compared to sham. B and T lymphopoiesis in the bone marrow and thymus was suppressed, and numbers of lymphocytes, CD4+, and CD8+ T cells in the spleen and MLN were all decreased in BO. Depletion of gut microbiota blocked BO-associated lymphopenia in the MLN. Corticosterone antagonism partially attenuated BO-associated reduction of lymphocytes in the thymus and bone marrow. Plasma OPN levels and OPN expression in the distended colon were increased in BO. Deletion of the OPN gene did not affect splenic lymphopenia, but attenuated suppression of lymphopoiesis in the bone marrow and thymus in BO.Conclusions: BO suppresses lymphocyte generation and maintenance in lymphoid organs. Mechanical distention-induced OPN, corticosterone, and gut microbiota are involved in the immune phenotype in BO.https://www.frontiersin.org/articles/10.3389/fphys.2022.1005088/fullintestinal obstructionmechanical stressosteopontincorticosteroneimmune dysfunctiongut microbiome |
| spellingShingle | You-Min Lin You-Min Lin Shrilakshmi Hegde Yingzi Cong Xuan-Zheng Shi Mechanisms of lymphoid depletion in bowel obstruction Frontiers in Physiology intestinal obstruction mechanical stress osteopontin corticosterone immune dysfunction gut microbiome |
| title | Mechanisms of lymphoid depletion in bowel obstruction |
| title_full | Mechanisms of lymphoid depletion in bowel obstruction |
| title_fullStr | Mechanisms of lymphoid depletion in bowel obstruction |
| title_full_unstemmed | Mechanisms of lymphoid depletion in bowel obstruction |
| title_short | Mechanisms of lymphoid depletion in bowel obstruction |
| title_sort | mechanisms of lymphoid depletion in bowel obstruction |
| topic | intestinal obstruction mechanical stress osteopontin corticosterone immune dysfunction gut microbiome |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.1005088/full |
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