IL-33 promotes anemia during chronic inflammation by inhibiting differentiation of erythroid progenitors
An important comorbidity of chronic inflammation is anemia, which may be related to dysregulated activity of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM). Among HSPCs, we found that the receptor for IL-33, ST2, is expressed preferentially and highly on erythroid progenitor...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Rockefeller University Press
2020
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| _version_ | 1826294030227472384 |
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| author | Swann, JW Koneva, LA Regan-Komito, D Sansom, SN Powrie, F Griseri, T |
| author_facet | Swann, JW Koneva, LA Regan-Komito, D Sansom, SN Powrie, F Griseri, T |
| author_sort | Swann, JW |
| collection | OXFORD |
| description | An important comorbidity of chronic inflammation is anemia, which may be related to dysregulated activity of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM). Among HSPCs, we found that the receptor for IL-33, ST2, is expressed preferentially and highly on erythroid progenitors. Induction of inflammatory spondyloarthritis in mice increased IL-33 in BM plasma, and IL-33 was required for inflammation-dependent suppression of erythropoiesis in BM. Conversely, administration of IL-33 in healthy mice suppressed erythropoiesis, decreased hemoglobin expression, and caused anemia. Using purified erythroid progenitors in vitro, we show that IL-33 directly inhibited terminal maturation. This effect was dependent on NF-κB activation and associated with altered signaling events downstream of the erythropoietin receptor. Accordingly, IL-33 also suppressed erythropoietin-accelerated erythropoiesis in vivo. These results reveal a role for IL-33 in pathogenesis of anemia during inflammatory disease and define a new target for its treatment. |
| first_indexed | 2024-03-07T03:39:20Z |
| format | Journal article |
| id | oxford-uuid:bd585791-95d9-4f63-a872-4aa061b8ad1c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:39:20Z |
| publishDate | 2020 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | oxford-uuid:bd585791-95d9-4f63-a872-4aa061b8ad1c2022-03-27T05:31:13ZIL-33 promotes anemia during chronic inflammation by inhibiting differentiation of erythroid progenitorsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bd585791-95d9-4f63-a872-4aa061b8ad1cEnglishSymplectic ElementsRockefeller University Press2020Swann, JWKoneva, LARegan-Komito, DSansom, SNPowrie, FGriseri, TAn important comorbidity of chronic inflammation is anemia, which may be related to dysregulated activity of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM). Among HSPCs, we found that the receptor for IL-33, ST2, is expressed preferentially and highly on erythroid progenitors. Induction of inflammatory spondyloarthritis in mice increased IL-33 in BM plasma, and IL-33 was required for inflammation-dependent suppression of erythropoiesis in BM. Conversely, administration of IL-33 in healthy mice suppressed erythropoiesis, decreased hemoglobin expression, and caused anemia. Using purified erythroid progenitors in vitro, we show that IL-33 directly inhibited terminal maturation. This effect was dependent on NF-κB activation and associated with altered signaling events downstream of the erythropoietin receptor. Accordingly, IL-33 also suppressed erythropoietin-accelerated erythropoiesis in vivo. These results reveal a role for IL-33 in pathogenesis of anemia during inflammatory disease and define a new target for its treatment. |
| spellingShingle | Swann, JW Koneva, LA Regan-Komito, D Sansom, SN Powrie, F Griseri, T IL-33 promotes anemia during chronic inflammation by inhibiting differentiation of erythroid progenitors |
| title | IL-33 promotes anemia during chronic inflammation by inhibiting differentiation of erythroid progenitors |
| title_full | IL-33 promotes anemia during chronic inflammation by inhibiting differentiation of erythroid progenitors |
| title_fullStr | IL-33 promotes anemia during chronic inflammation by inhibiting differentiation of erythroid progenitors |
| title_full_unstemmed | IL-33 promotes anemia during chronic inflammation by inhibiting differentiation of erythroid progenitors |
| title_short | IL-33 promotes anemia during chronic inflammation by inhibiting differentiation of erythroid progenitors |
| title_sort | il 33 promotes anemia during chronic inflammation by inhibiting differentiation of erythroid progenitors |
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