Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes.
Mice deficient in the transcription factor Runx3 develop a multitude of immune system defects, including early onset colitis. This paper demonstrates that Runx3 is expressed in colonic mononuclear phagocytes (MNP), including resident macrophages (RM) and dendritic cell subsets (cDC2). Runx3 deletion...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0233044 |
| _version_ | 1818833825787019264 |
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| author | Shay Hantisteanu Yosef Dicken Varda Negreanu Dalia Goldenberg Ori Brenner Dena Leshkowitz Joseph Lotem Ditsa Levanon Yoram Groner |
| author_facet | Shay Hantisteanu Yosef Dicken Varda Negreanu Dalia Goldenberg Ori Brenner Dena Leshkowitz Joseph Lotem Ditsa Levanon Yoram Groner |
| author_sort | Shay Hantisteanu |
| collection | DOAJ |
| description | Mice deficient in the transcription factor Runx3 develop a multitude of immune system defects, including early onset colitis. This paper demonstrates that Runx3 is expressed in colonic mononuclear phagocytes (MNP), including resident macrophages (RM) and dendritic cell subsets (cDC2). Runx3 deletion in MNP causes early onset colitis due to their impaired maturation. Mechanistically, the resulting MNP subset imbalance leads to up-regulation of pro-inflammatory genes as occurs in IL10R-deficient RM. In addition, RM and cDC2 display a marked decrease in expression of anti-inflammatory/TGF β-regulated genes and β-catenin signaling associated genes, respectively. MNP transcriptome and ChIP-seq data analysis suggest that a significant fraction of genes affected by Runx3 loss are direct Runx3 targets. Collectively, Runx3 imposes intestinal immune tolerance by regulating maturation of colonic anti-inflammatory MNP, befitting the identification of RUNX3 as a genome-wide associated risk gene for various immune-related diseases in humans, including gastrointestinal tract diseases such as Crohn's disease and celiac. |
| first_indexed | 2024-12-19T02:25:05Z |
| format | Article |
| id | doaj.art-25c2dace29424c76a8efa78a71181e1d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T02:25:05Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-25c2dace29424c76a8efa78a71181e1d2022-12-21T20:39:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01155e023304410.1371/journal.pone.0233044Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes.Shay HantisteanuYosef DickenVarda NegreanuDalia GoldenbergOri BrennerDena LeshkowitzJoseph LotemDitsa LevanonYoram GronerMice deficient in the transcription factor Runx3 develop a multitude of immune system defects, including early onset colitis. This paper demonstrates that Runx3 is expressed in colonic mononuclear phagocytes (MNP), including resident macrophages (RM) and dendritic cell subsets (cDC2). Runx3 deletion in MNP causes early onset colitis due to their impaired maturation. Mechanistically, the resulting MNP subset imbalance leads to up-regulation of pro-inflammatory genes as occurs in IL10R-deficient RM. In addition, RM and cDC2 display a marked decrease in expression of anti-inflammatory/TGF β-regulated genes and β-catenin signaling associated genes, respectively. MNP transcriptome and ChIP-seq data analysis suggest that a significant fraction of genes affected by Runx3 loss are direct Runx3 targets. Collectively, Runx3 imposes intestinal immune tolerance by regulating maturation of colonic anti-inflammatory MNP, befitting the identification of RUNX3 as a genome-wide associated risk gene for various immune-related diseases in humans, including gastrointestinal tract diseases such as Crohn's disease and celiac.https://doi.org/10.1371/journal.pone.0233044 |
| spellingShingle | Shay Hantisteanu Yosef Dicken Varda Negreanu Dalia Goldenberg Ori Brenner Dena Leshkowitz Joseph Lotem Ditsa Levanon Yoram Groner Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes. PLoS ONE |
| title | Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes. |
| title_full | Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes. |
| title_fullStr | Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes. |
| title_full_unstemmed | Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes. |
| title_short | Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes. |
| title_sort | runx3 prevents spontaneous colitis by directing the differentiation of anti inflammatory mononuclear phagocytes |
| url | https://doi.org/10.1371/journal.pone.0233044 |
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