Dysregulated Hematopoietic Stem and Progenitor Cell Activity Promotes Interleukin-23-Driven Chronic Intestinal Inflammation
In interleukin-23 (IL-23)-dependent colitis, there is excessive accumulation of short-lived neutrophils and inflammatory monocytes in the intestine. It is unknown whether this reflects changes in mature cell populations or whether the IL-23-driven colitogenic T cell program regulates upstream hemato...
| Main Authors: | , , , |
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| Format: | Journal article |
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2012
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| _version_ | 1797067793192976384 |
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| author | Griseri, T McKenzie, B Schiering, C Powrie, F |
| author_facet | Griseri, T McKenzie, B Schiering, C Powrie, F |
| author_sort | Griseri, T |
| collection | OXFORD |
| description | In interleukin-23 (IL-23)-dependent colitis, there is excessive accumulation of short-lived neutrophils and inflammatory monocytes in the intestine. It is unknown whether this reflects changes in mature cell populations or whether the IL-23-driven colitogenic T cell program regulates upstream hematopoietic stem and progenitor cells (HSPC). Here we have shown dysregulation of hematopoiesis in colitis mediated by inflammatory cytokines. First, there was an interferon-gamma-dependent accumulation of proliferating hematopoietic stem cells in the bone marrow and spleen. Second, there was a strong skew toward granulocyte-monocyte progenitor (GMP) production at the expense of erythroid and lymphoid progenitors. Extramedullary hematopoiesis was also evident, and granulocyte macrophage-colony stimulating factor (GM-CSF) blockade reduced the accumulation of splenic and colonic GMPs, resulting in amelioration of colitis. Importantly, transfer of GMPs exacerbated colitis. These data identify HSPCs as a major target of the IL-23-driven inflammatory axis suggesting therapeutic strategies for the treatment of inflammatory bowel disease. © 2012 Elsevier Inc. |
| first_indexed | 2024-03-06T22:01:26Z |
| format | Journal article |
| id | oxford-uuid:4eba439b-bb40-4e21-8447-8268d635d12f |
| institution | University of Oxford |
| last_indexed | 2024-03-06T22:01:26Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:4eba439b-bb40-4e21-8447-8268d635d12f2022-03-26T16:02:55ZDysregulated Hematopoietic Stem and Progenitor Cell Activity Promotes Interleukin-23-Driven Chronic Intestinal InflammationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4eba439b-bb40-4e21-8447-8268d635d12fSymplectic Elements at Oxford2012Griseri, TMcKenzie, BSchiering, CPowrie, FIn interleukin-23 (IL-23)-dependent colitis, there is excessive accumulation of short-lived neutrophils and inflammatory monocytes in the intestine. It is unknown whether this reflects changes in mature cell populations or whether the IL-23-driven colitogenic T cell program regulates upstream hematopoietic stem and progenitor cells (HSPC). Here we have shown dysregulation of hematopoiesis in colitis mediated by inflammatory cytokines. First, there was an interferon-gamma-dependent accumulation of proliferating hematopoietic stem cells in the bone marrow and spleen. Second, there was a strong skew toward granulocyte-monocyte progenitor (GMP) production at the expense of erythroid and lymphoid progenitors. Extramedullary hematopoiesis was also evident, and granulocyte macrophage-colony stimulating factor (GM-CSF) blockade reduced the accumulation of splenic and colonic GMPs, resulting in amelioration of colitis. Importantly, transfer of GMPs exacerbated colitis. These data identify HSPCs as a major target of the IL-23-driven inflammatory axis suggesting therapeutic strategies for the treatment of inflammatory bowel disease. © 2012 Elsevier Inc. |
| spellingShingle | Griseri, T McKenzie, B Schiering, C Powrie, F Dysregulated Hematopoietic Stem and Progenitor Cell Activity Promotes Interleukin-23-Driven Chronic Intestinal Inflammation |
| title | Dysregulated Hematopoietic Stem and Progenitor Cell Activity Promotes Interleukin-23-Driven Chronic Intestinal Inflammation |
| title_full | Dysregulated Hematopoietic Stem and Progenitor Cell Activity Promotes Interleukin-23-Driven Chronic Intestinal Inflammation |
| title_fullStr | Dysregulated Hematopoietic Stem and Progenitor Cell Activity Promotes Interleukin-23-Driven Chronic Intestinal Inflammation |
| title_full_unstemmed | Dysregulated Hematopoietic Stem and Progenitor Cell Activity Promotes Interleukin-23-Driven Chronic Intestinal Inflammation |
| title_short | Dysregulated Hematopoietic Stem and Progenitor Cell Activity Promotes Interleukin-23-Driven Chronic Intestinal Inflammation |
| title_sort | dysregulated hematopoietic stem and progenitor cell activity promotes interleukin 23 driven chronic intestinal inflammation |
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