Dendritic Cell Subsets in Intestinal Immunity and Inflammation

Sun, Tian; Nguyen, Albert; Gommerman, Jennifer L.

doi:10.4049/jimmunol.1900710

Cited by 69 publications

(53 citation statements)

References 154 publications

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“…Intestinal dendritic cells are a heterogeneous population of resident innate immune cells located in organized lymphoid tissue, such as Peyer's patches and the lamina propria, with various functions ranging from antigen presentation, mediating oral tolerance and initiating immune responses. 47 Recently, DCs have been found to regulate intestinal homoeostasis through TGF-β signalling by modulating mucus production and disease severity in Dextran Sulfate Sodium (DSS)-induced colitis through Notch signalling. 48 Other myeloid cells, including macrophages and neutrophils, have also been identified as major contributors to IEC homoeostasis and inflammation.…”

Section: Cellular Component Of the Intestinal Barriermentioning

confidence: 99%

“…These so‐called M cells line the luminal surface of Peyer’s patches and take up antigens or microorganisms directly from the lumen to facilitate their transportation and presentation to underlying resident immune cells. Intestinal dendritic cells are a heterogeneous population of resident innate immune cells located in organized lymphoid tissue, such as Peyer’s patches and the lamina propria, with various functions ranging from antigen presentation, mediating oral tolerance and initiating immune responses 47 . Recently, DCs have been found to regulate intestinal homoeostasis through TGF‐β signalling by modulating mucus production and disease severity in Dextran Sulfate Sodium (DSS)‐induced colitis through Notch signalling 48 .…”

Section: Overview Of the Composition Of The Intestinal Barriermentioning

confidence: 99%

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Targeting desmosomal adhesion and signalling for intestinal barrier stabilization in inflammatory bowel diseases—Lessons from experimental models and patients

2020

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Inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) and Ulcerative colitis (UC) have a complex and multifactorial pathogenesis which is incompletely understood. A typical feature closely associated with clinical symptoms is impaired intestinal epithelial barrier function. Mounting evidence suggests that desmosomes, which together with tight junctions (TJ) and adherens junctions (AJ) form the intestinal epithelial barrier, play a distinct role in IBD pathogenesis. This is based on the finding that desmoglein (Dsg) 2, a cadherin‐type adhesion molecule of desmosomes, is required for maintenance of intestinal barrier properties both in vitro and in vivo, presumably via Dsg2‐mediated regulation of TJ. Mice deficient for intestinal Dsg2 show increased basal permeability and are highly susceptible to experimental colitis. In several cohorts of IBD patients, intestinal protein levels of Dsg2 are reduced and desmosome ultrastructure is altered suggesting that Dsg2 is involved in IBD pathogenesis. In addition to its adhesive function, Dsg2 contributes to enterocyte cohesion and intestinal barrier function. Dsg2 is also involved in enterocyte proliferation, barrier differentiation and induction of apoptosis, in part by regulation of p38MAPK and EGFR signalling. In IBD, the function of Dsg2 appears to be compromised via p38MAPK activation, which is a critical pathway for regulation of desmosomes and is associated with keratin phosphorylation in IBD patients. In this review, the current findings on the role of Dsg2 as a novel promising target to prevent loss of intestinal barrier function in IBD patients are discussed.

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Section: Cellular Component Of the Intestinal Barriermentioning

confidence: 99%

Section: Overview Of the Composition Of The Intestinal Barriermentioning

confidence: 99%

Targeting desmosomal adhesion and signalling for intestinal barrier stabilization in inflammatory bowel diseases—Lessons from experimental models and patients

2020

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“…In the colon, DCs are divided into three groups: CD103 + CD11b − , CD103 + CD11b + , and CD103 − CD11b + DCs. These cells coordinately control colonic immune homeostasis, allowing an optimal response to commensal bacteria and food antigens 31 . RIPK1 was equally expressed in these three subsets (Fig.…”

Section: Resultsmentioning

confidence: 99%

The scaffold-dependent function of RIPK1 in dendritic cells promotes injury-induced colitis

Moriwaki

Park

Koyama

et al. 2021

Preprint

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Receptor interacting protein kinase 1 (RIPK1) is a cytosolic multidomain protein that controls cell life and death. While RIPK1 promotes cell death through its kinase activity, it also functions as a scaffold protein to promote cell survival by inhibiting FADD-caspase 8-dependent apoptosis and RIPK3-MLKL-dependent necroptosis. This pro-survival function is highlighted by excess cell death and a perinatal lethality in Ripk1-/- mice. Recently, loss of function mutation of RIPK1 was found in patients with immunodeficiency and inflammatory bowel diseases. Hematopoietic stem cell transplantation restored not only immunodeficiency but also intestinal inflammatory pathology, indicating that RIPK1 in hematopoietic cells is critical to maintain intestinal immune homeostasis. Here, we generated dendritic cell (DC)-specific Ripk1-/- mice in a genetic background with loss of RIPK1 kinase activity and found that the mice developed spontaneous colonic inflammation characterized by increased neutrophil infiltration. In addition, these mice were highly resistant to injury-induced colitis. The increased neutrophil infiltration in the colon and the resistance to colitis were restored by dual inactivation of RIPK3 and FADD, but not by inhibition of RIPK3, MLKL, or ZBP1 alone. Altogether, these results reveal a scaffold activity-dependent role of RIPK1 in protecting colonic DCs from apoptotic insults and maintenance of colonic immune homeostasis.

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“…Microbial or microbial component translocation through the intestinal mucosa can result in dendritic cell (DC) activation and inflammatory cytokines secretion [ 1 ]; this response needs to be limited to facilitate tissue repair and a return to intestinal homeostasis; if prolonged, chronic inflammation may arise and progress toward inflammatory bowel diseases (IBDs) [ 2 , 3 , 4 ]. Therefore, DCs residing in the gut-associated lymphoid tissues (GALT) are involved in the maintenance of tolerance toward the commensal microbiota that has a pivotal role in the development of IBDs [ 5 ]. These include ulcerative colitis and Crohn’s disease, which are characterized by epithelial barrier dysfunction [ 6 ] that may expose mucosal resident DCs to abundant luminal-derived lipopolysaccharide (LPS) and consequent excessive activation of immune cells besides the secretion of pro-inflammatory cytokines [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Quercetin Administration Suppresses the Cytokine Storm in Myeloid and Plasmacytoid Dendritic Cells

Verna

Liso

Cavalcanti

et al. 2021

IJMS

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Dendritic cells (DCs) can be divided by lineage into myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). They both are present in mucosal tissues and regulate the immune response by secreting chemokines and cytokines. Inflammatory bowel diseases (IBDs) are characterized by a leaky intestinal barrier and the consequent translocation of bacterial lipopolysaccharide (LPS) to the basolateral side. This results in DCs activation, but the response of pDCs is still poorly characterized. In the present study, we compared mDCs and pDCs responses to LPS administration. We present a broad panel of DCs secreted factors, including cytokines, chemokines, and growth factors. Our recent studies demonstrated the anti-inflammatory effects of quercetin administration, but to date, there is no evidence about quercetin’s effects on pDCs. The results of the present study demonstrate that pDCs can respond to LPS and that quercetin exposure modulates soluble factors release through the same molecular pathway used by mDCs (Slpi, Hmox1, and AP-1).

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Dendritic Cell Subsets in Intestinal Immunity and Inflammation

Cited by 69 publications

References 154 publications

Targeting desmosomal adhesion and signalling for intestinal barrier stabilization in inflammatory bowel diseases—Lessons from experimental models and patients

Targeting desmosomal adhesion and signalling for intestinal barrier stabilization in inflammatory bowel diseases—Lessons from experimental models and patients

The scaffold-dependent function of RIPK1 in dendritic cells promotes injury-induced colitis

Quercetin Administration Suppresses the Cytokine Storm in Myeloid and Plasmacytoid Dendritic Cells

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