Intestinal dendritic cells

Abstract

Dendritic cells (DCs) play a key role in discriminating between commensal microorganisms and potentially harmful pathogens and in maintaining the balance between tolerance and active immunity. The regulatory role of DC is of particular importance in the gut where the immune system lies in intimate contact with the highly antigenic external environment. Intestinal DC constantly survey the luminal microenvironment. They act as sentinels, acquiring antigens in peripheral tissues before migrating to secondary lymphoid organs to activate naive T cells. They are also sensors, responding to a spectrum of environmental cues by extensive differentiation or maturation. Recent studies have begun to elucidate mechanisms for functional specializations of DC in the intestine that may include the involvement of retinoic acid and transforming growth factor-β. Specialized CD103(+) intestinal DC can promote the differentiation of Foxp3(+) regulatory T cells via a retinoic acid-dependent process. Different DC outcomes are, in part, influenced by their exposure to microbial stimuli. Evidence is also emerging of the close interaction between bacteria, epithelial cells, and DC in the maintenance of intestinal immune homeostasis. Here we review recent advances of functionally specialized intestinal DC and their mechanisms of antigen uptake and recognition. We also discuss the interaction of DC with intestinal microbiota and their ability to orchestrate protective immunity and immune tolerance in the host. Lastly, we describe how DC functions are altered in intestinal inflammation and their emerging potential as a therapeutic target in inflammatory bowel disease.

Long term effect of gut microbiota transfer on diabetes development

“…Gut bacteria shape immune homeostasis and influence the generation of regulatory T cells [37]. Antigen-presenting cells within the gut are directly affected [38], with recent evidence suggesting that particular metabolites such as short-chain fatty acids are key players [39, 40]. We have shown that the mice transferred with the MyD88−/−NOD microbiota expressed regulatory immune responses in the gut, with increased IgA and TGFβ as well as a considerable increase in a population of CD8 + CD103 + T cells which have been identified to be a regulatory CD8 population [41].…”

Functional Specialization of Islet Dendritic Cell Subsets

“…CD103 + DC are derived exclusively from pre-DC under the control of fms-like tyrosine kinase 3 (Flt3) ligand and its receptor Flt3, whereas CD103 − DC are a heterogeneous population dependent on both Flt3 and macrophage colony-stimulating factor receptor (MCSF-R) (7–9). The two DC subsets have different functions in the intestine and lung (8, 9, 11, 12). Lamina propria CX3CR1 + CD103 − DC sample intestinal antigens by projecting dendrites through the epithelial cell layer and into the lumen, may serve as a first line of defense by phagocytosing and killing bacteria (13–16).…”

Gut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells

“…CD103 + LP DCs preferentially promote the differentiation of Treg cells 12, 13 , whereas CX 3 CR1 + LP DCs and microphages can induce Th1 and Th17 development in the gut. To determine whether there were altered mucosal CD4 + T cell subsets upon deletion of gp96 from CD11c + APCs, we isolated cLP from KO mice and WT littermates, followed by examination of T cell subsets.…”

“…CD103 + intestinal DCs consist of CD103 + CD11b + DCs controlled by the transcription factors IRF4 and Notch2 8–10 and CD103 + CD11b − DCs that require BATF3 and IRF8 for their respective development 11 . CD103 + DCs preferentially promote the differentiation of Foxp3 + regulatory T (Treg) cells to maintain tolerance 12–14 . In addition, a recent study showed that CD103 + CD11b − DCs are required for peripheral Treg cell induction during dietary antigen exposure 2 .…”