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...
| Հիմնական հեղինակներ: | , , , |
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| Ձևաչափ: | Conference item |
| Հրապարակվել է: |
2012
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| _version_ | 1826272283376746496 |
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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. |
| first_indexed | 2024-03-06T22:10:06Z |
| format | Conference item |
| id | oxford-uuid:5183c98d-7b64-46ae-86c4-dfab1ee4b58a |
| institution | University of Oxford |
| last_indexed | 2024-03-06T22:10:06Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:5183c98d-7b64-46ae-86c4-dfab1ee4b58a2022-03-26T16:20:00ZDysregulated hematopoietic stem and progenitor cell activity promotes interleukin-23-driven chronic intestinal inflammation.Conference itemhttp://purl.org/coar/resource_type/c_5794uuid:5183c98d-7b64-46ae-86c4-dfab1ee4b58aSymplectic 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. |
| 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 |
| work_keys_str_mv | AT griserit dysregulatedhematopoieticstemandprogenitorcellactivitypromotesinterleukin23drivenchronicintestinalinflammation AT mckenzieb dysregulatedhematopoieticstemandprogenitorcellactivitypromotesinterleukin23drivenchronicintestinalinflammation AT schieringc dysregulatedhematopoieticstemandprogenitorcellactivitypromotesinterleukin23drivenchronicintestinalinflammation AT powrief dysregulatedhematopoieticstemandprogenitorcellactivitypromotesinterleukin23drivenchronicintestinalinflammation |