A20 in dendritic cells restrains intestinal anti-bacterial peptide expression and preserves commensal homeostasis.
Microbial dysbiosis commonly occurs in patients with inflammatory bowel diseases (IBD). Exogenous causes of dysbiosis such as antibiotics and diet are well described, but host derived causes are understudied. A20 is a potent regulator of signals triggered by microbial pattern molecules, and A20 regu...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0218999 |
| _version_ | 1797660697321013248 |
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| author | Alice Talpin Michael G Kattah Rommel Advincula Douglas Fadrosh Kole Lynch Brandon LaMere Kei E Fujimura Nabeetha A Nagalingam Barbara A Malynn Susan V Lynch Averil Ma |
| author_facet | Alice Talpin Michael G Kattah Rommel Advincula Douglas Fadrosh Kole Lynch Brandon LaMere Kei E Fujimura Nabeetha A Nagalingam Barbara A Malynn Susan V Lynch Averil Ma |
| author_sort | Alice Talpin |
| collection | DOAJ |
| description | Microbial dysbiosis commonly occurs in patients with inflammatory bowel diseases (IBD). Exogenous causes of dysbiosis such as antibiotics and diet are well described, but host derived causes are understudied. A20 is a potent regulator of signals triggered by microbial pattern molecules, and A20 regulates susceptibility to intestinal inflammation in mice and in humans. We now report that mice lacking A20 expression in dendritic cells, A20FL/FL CD11c-Cre mice (or A20dDC mice), spontaneously develop colitogenic intestinal dysbiosis that is evident upon weaning and precedes the onset of colitis. Intestines from A20dDC mice express increased amounts of Reg3β and Reg3γ, but not Ang4. A20 deficient DCs promote gut microbiota perturbation in the absence of adaptive lymphocytes. Moreover, A20 deficient DCs directly induce expression of Reg3β and Reg3γ but not Ang 4 in normal intestinal epithelial cell enteroid cultures in the absence of other cell types. These findings reveal a pathophysiological pathway in which defective expression of an IBD susceptibility gene in DCs drives aberrant expression of anti-bacterial peptides and luminal dysbiosis that in turn confers host susceptibility to intestinal inflammation. |
| first_indexed | 2024-03-11T18:34:43Z |
| format | Article |
| id | doaj.art-2fb8e9cbe26c4c2dae970efafca2d269 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-11T18:34:43Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2fb8e9cbe26c4c2dae970efafca2d2692023-10-13T05:31:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01147e021899910.1371/journal.pone.0218999A20 in dendritic cells restrains intestinal anti-bacterial peptide expression and preserves commensal homeostasis.Alice TalpinMichael G KattahRommel AdvinculaDouglas FadroshKole LynchBrandon LaMereKei E FujimuraNabeetha A NagalingamBarbara A MalynnSusan V LynchAveril MaMicrobial dysbiosis commonly occurs in patients with inflammatory bowel diseases (IBD). Exogenous causes of dysbiosis such as antibiotics and diet are well described, but host derived causes are understudied. A20 is a potent regulator of signals triggered by microbial pattern molecules, and A20 regulates susceptibility to intestinal inflammation in mice and in humans. We now report that mice lacking A20 expression in dendritic cells, A20FL/FL CD11c-Cre mice (or A20dDC mice), spontaneously develop colitogenic intestinal dysbiosis that is evident upon weaning and precedes the onset of colitis. Intestines from A20dDC mice express increased amounts of Reg3β and Reg3γ, but not Ang4. A20 deficient DCs promote gut microbiota perturbation in the absence of adaptive lymphocytes. Moreover, A20 deficient DCs directly induce expression of Reg3β and Reg3γ but not Ang 4 in normal intestinal epithelial cell enteroid cultures in the absence of other cell types. These findings reveal a pathophysiological pathway in which defective expression of an IBD susceptibility gene in DCs drives aberrant expression of anti-bacterial peptides and luminal dysbiosis that in turn confers host susceptibility to intestinal inflammation.https://doi.org/10.1371/journal.pone.0218999 |
| spellingShingle | Alice Talpin Michael G Kattah Rommel Advincula Douglas Fadrosh Kole Lynch Brandon LaMere Kei E Fujimura Nabeetha A Nagalingam Barbara A Malynn Susan V Lynch Averil Ma A20 in dendritic cells restrains intestinal anti-bacterial peptide expression and preserves commensal homeostasis. PLoS ONE |
| title | A20 in dendritic cells restrains intestinal anti-bacterial peptide expression and preserves commensal homeostasis. |
| title_full | A20 in dendritic cells restrains intestinal anti-bacterial peptide expression and preserves commensal homeostasis. |
| title_fullStr | A20 in dendritic cells restrains intestinal anti-bacterial peptide expression and preserves commensal homeostasis. |
| title_full_unstemmed | A20 in dendritic cells restrains intestinal anti-bacterial peptide expression and preserves commensal homeostasis. |
| title_short | A20 in dendritic cells restrains intestinal anti-bacterial peptide expression and preserves commensal homeostasis. |
| title_sort | a20 in dendritic cells restrains intestinal anti bacterial peptide expression and preserves commensal homeostasis |
| url | https://doi.org/10.1371/journal.pone.0218999 |
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