Plasmacytoid Dendritic Cells Are Largely Dispensable for the Pathogenesis of Experimental Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by an aberrant immune response to microbial components of the gastrointestinal tract. Plasmacytoid dendritic cells (pDCs) are innate immune cells specialized in the production of type I interferons and were recently implicat...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02475/full |
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| author | Catherine M. Sawai Catherine M. Sawai Lee Serpas Antonio Galvao Neto Geunhyo Jang Ali Rashidfarrokhi Roland Kolbeck Miguel A. Sanjuan Boris Reizis Boris Reizis Vanja Sisirak Vanja Sisirak |
| author_facet | Catherine M. Sawai Catherine M. Sawai Lee Serpas Antonio Galvao Neto Geunhyo Jang Ali Rashidfarrokhi Roland Kolbeck Miguel A. Sanjuan Boris Reizis Boris Reizis Vanja Sisirak Vanja Sisirak |
| author_sort | Catherine M. Sawai |
| collection | DOAJ |
| description | Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by an aberrant immune response to microbial components of the gastrointestinal tract. Plasmacytoid dendritic cells (pDCs) are innate immune cells specialized in the production of type I interferons and were recently implicated in the pathogenesis of autoimmune disorders such as lupus and scleroderma. While pDCs were shown to infiltrate intestinal mucosa of IBD patients and proposed to participate in intestinal inflammation, their net contribution to the disease remains unclear. We addressed this question by targeting the pDC-specific transcription factor TCF4 (E2-2) in experimental IBD caused by deficiency of Wiskott-Aldrich syndrome protein (WASP) or of interleukin-10 (IL-10). Monoallelic Tcf4 deletion, which was previously shown to abrogate experimental lupus, did not affect autoimmunity manifestations or colitis in WASP-deficient animals. Furthermore, conditional biallelic Tcf4 targeting resulted in a near-complete pDC ablation, yet had no effect on the development of colitis in IL-10-deficient mice. Our results suggest that, in contrast to other inflammatory and autoimmune diseases, pDCs do not play a major role in the pathogenesis of intestinal inflammation during IBD. |
| first_indexed | 2024-12-12T21:00:07Z |
| format | Article |
| id | doaj.art-fcd7d50faba946528fda964f57409e43 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T21:00:07Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fcd7d50faba946528fda964f57409e432022-12-22T00:12:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-10-01910.3389/fimmu.2018.02475415131Plasmacytoid Dendritic Cells Are Largely Dispensable for the Pathogenesis of Experimental Inflammatory Bowel DiseaseCatherine M. Sawai0Catherine M. Sawai1Lee Serpas2Antonio Galvao Neto3Geunhyo Jang4Ali Rashidfarrokhi5Roland Kolbeck6Miguel A. Sanjuan7Boris Reizis8Boris Reizis9Vanja Sisirak10Vanja Sisirak11Department of Pathology, New York University School of Medicine, New York, NY, United StatesINSERM, ACTION Laboratory, University of Bordeaux, Bordeaux, FranceDepartment of Pathology, New York University School of Medicine, New York, NY, United StatesDepartment of Pathology, New York University School of Medicine, New York, NY, United StatesDepartment of Pathology, New York University School of Medicine, New York, NY, United StatesDepartment of Pathology, New York University School of Medicine, New York, NY, United StatesDepartment of Respiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, MD, United StatesDepartment of Respiratory, Inflammation and Autoimmunity, MedImmune LLC, Gaithersburg, MD, United StatesDepartment of Pathology, New York University School of Medicine, New York, NY, United StatesDepartment of Medicine, New York University School of Medicine, New York, NY, United StatesDepartment of Pathology, New York University School of Medicine, New York, NY, United StatesCNRS-UMR, Immunoconcept, Université de Bordeaux, Bordeaux, FranceInflammatory bowel disease (IBD) is a chronic inflammatory condition caused by an aberrant immune response to microbial components of the gastrointestinal tract. Plasmacytoid dendritic cells (pDCs) are innate immune cells specialized in the production of type I interferons and were recently implicated in the pathogenesis of autoimmune disorders such as lupus and scleroderma. While pDCs were shown to infiltrate intestinal mucosa of IBD patients and proposed to participate in intestinal inflammation, their net contribution to the disease remains unclear. We addressed this question by targeting the pDC-specific transcription factor TCF4 (E2-2) in experimental IBD caused by deficiency of Wiskott-Aldrich syndrome protein (WASP) or of interleukin-10 (IL-10). Monoallelic Tcf4 deletion, which was previously shown to abrogate experimental lupus, did not affect autoimmunity manifestations or colitis in WASP-deficient animals. Furthermore, conditional biallelic Tcf4 targeting resulted in a near-complete pDC ablation, yet had no effect on the development of colitis in IL-10-deficient mice. Our results suggest that, in contrast to other inflammatory and autoimmune diseases, pDCs do not play a major role in the pathogenesis of intestinal inflammation during IBD.https://www.frontiersin.org/article/10.3389/fimmu.2018.02475/fullPlasmacytoid dendritic cell (PDC)Interferon Type IcolitisInflammatory bowel disease (IBD)autoimmune disease |
| spellingShingle | Catherine M. Sawai Catherine M. Sawai Lee Serpas Antonio Galvao Neto Geunhyo Jang Ali Rashidfarrokhi Roland Kolbeck Miguel A. Sanjuan Boris Reizis Boris Reizis Vanja Sisirak Vanja Sisirak Plasmacytoid Dendritic Cells Are Largely Dispensable for the Pathogenesis of Experimental Inflammatory Bowel Disease Frontiers in Immunology Plasmacytoid dendritic cell (PDC) Interferon Type I colitis Inflammatory bowel disease (IBD) autoimmune disease |
| title | Plasmacytoid Dendritic Cells Are Largely Dispensable for the Pathogenesis of Experimental Inflammatory Bowel Disease |
| title_full | Plasmacytoid Dendritic Cells Are Largely Dispensable for the Pathogenesis of Experimental Inflammatory Bowel Disease |
| title_fullStr | Plasmacytoid Dendritic Cells Are Largely Dispensable for the Pathogenesis of Experimental Inflammatory Bowel Disease |
| title_full_unstemmed | Plasmacytoid Dendritic Cells Are Largely Dispensable for the Pathogenesis of Experimental Inflammatory Bowel Disease |
| title_short | Plasmacytoid Dendritic Cells Are Largely Dispensable for the Pathogenesis of Experimental Inflammatory Bowel Disease |
| title_sort | plasmacytoid dendritic cells are largely dispensable for the pathogenesis of experimental inflammatory bowel disease |
| topic | Plasmacytoid dendritic cell (PDC) Interferon Type I colitis Inflammatory bowel disease (IBD) autoimmune disease |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02475/full |
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