Dendritic cells in intestinal immune regulation

Coombes, Janine L.; Powrie, Fiona

doi:10.1038/nri2335

Cited by 678 publications

(679 citation statements)

References 117 publications

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“…Upon migration to mesenteric LN, CD103 1 DC confer gutseeking properties upon antigen-responsive T cells via production of RA [24,25]. Importantly, RA production by gut-associated DC is also involved in the generation of induced Foxp3 1 Treg (iTreg) [13,26]. Although ''naturally occurring'' Foxp3 1 Treg develop in the thymus, iTreg develop de novo in secondary lymphoid organs from conventional naïve CD4 1 T cells.…”

Section: Role Of Skin DC In the Induction Of Foxp3 1 Tregmentioning

confidence: 99%

“…Inf-DC appear not only to produce high levels of microbicidal compounds but also to perform functions distinct from those carried out by the DC present under non-inflammatory conditions. In the absence of inflammation, tissues such as the gut and the skin are believed to ''condition'' DC in a way that prevents DC from inducing Th1 responses [13]. By differentiating from monocytes in an extemporaneous manner, inf-DC might escape such conditioning and thus be the only DC capable of activating effector T cells at the site of infection and, following migration to LN, be the DC capable of polarizing naïve CD4 1 T cells toward a Th1 fate.…”

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confidence: 99%

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From skin dendritic cells to a simplified classification of human and mouse dendritic cell subsets

et al. 2010

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Recent studies have identified several DC subsets within the mouse skin and showed that functional specialization exists among them. This Viewpoint summarizes recent data on functional specialization of skin DC subsets and integrates this knowledge into a unifying DC classification that emphasizes the similarities between the DC subsets found in both lymphoid and nonlymphoid tissues of several mammalian species.

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Section: Role Of Skin DC In the Induction Of Foxp3 1 Tregmentioning

confidence: 99%

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confidence: 99%

From skin dendritic cells to a simplified classification of human and mouse dendritic cell subsets

et al. 2010

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“…Alternatively, tissue-resident DC may adopt distinct functions under homeostatic and inflammatory conditions [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…One possibility is that these activities are mediated by distinct DC populations and indeed many subtypes of DC have been identified in the gut [4]. It has been proposed that resident gutconditioned DC may favour tolerogenic responses, whereas newly recruited inflammatory DC may drive host protective immunity.Alternatively, tissue-resident DC may adopt distinct functions under homeostatic and inflammatory conditions [4,5].We and others [6][7][8][9] have identified and characterised a specialised population of MLN DC that express the integrin a E chain, CD103. CD103 1 DC represent a sentinel DC population in the small intestine (SI) and can migrate to the MLN to initiate adaptive immune responses [10].…”

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confidence: 98%

Intestinal inflammation abrogates the tolerogenic properties of MLN CD103⁺ dendritic cells

Laffont¹,

Siddiqui²,

2010

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Intestinal CD103 1 DC promote the differentiation of Foxp3 1 Treg from naïve CD4 1 T cells through mechanisms involving TGF-b and the dietary metabolite, retinoic acid (RA). In this study, we have analysed whether the specialised features of CD103 1 DC are conserved in colitis. Our results show that inflammation dampens the tolerogenic properties of MLN CD103 1 DC, which is associated with lower expression of tgfb2 and aldh1a2. Accordingly, CD103 1 DC taken from colitic mice are impaired in their ability to induce Foxp3 1 Treg and instead favour the emergence of IFN-c-producing CD4 1 T cells compared with their steady-state counterparts. BrdU-labelling studies and analysis of ontogeny markers show that CD103 1 DC from steady-state and colitic settings retain similar subset composition and developmental pathways. These results indicate that MLN CD103 1 DC are not hard-wired to promote tolerance but can adapt to environmental conditions. The inflammatory properties of MLN CD103 1 DC in colitic mice may reflect defective gut tolerogenic conditioning or altered migratory pathways and raise the possibility that migratory DC populations contribute to the pathogenesis of inflammatory bowel disease.Key words: Colitis . DC . Intestinal immunity . Ontogeny . Treg IntroductionThe intestinal immune system must maintain a fine balance between harmless responses to food and commensal bacteria and protective immunity to invading pathogens. It is now well established that DC play a central role in orchestrating intestinal immune responses through promotion of inflammatory pathways and the maintenance of tolerance [1][2][3]. Precisely, how DC mediate these diverse and opposing functions is not known. One possibility is that these activities are mediated by distinct DC populations and indeed many subtypes of DC have been identified in the gut [4]. It has been proposed that resident gutconditioned DC may favour tolerogenic responses, whereas newly recruited inflammatory DC may drive host protective immunity.Alternatively, tissue-resident DC may adopt distinct functions under homeostatic and inflammatory conditions [4,5].We and others [6][7][8][9] have identified and characterised a specialised population of MLN DC that express the integrin a E chain, CD103. CD103 1 DC represent a sentinel DC population in the small intestine (SI) and can migrate to the MLN to initiate adaptive immune responses [10]. Under homeostatic conditions, CD103 1 DC in MLN promote the development of Foxp3 1 Treg. By contrast, the reciprocal CD103 À MLN DC population displays a more pro-inflammatory phenotype and appears to represent a developmentally distinct DC population [9].In intestinal inflammation, immune regulatory pathways that normally promote tolerance in the intestine break down. Whether this is attributable to changes in DC populations or their function in the MLN is not known. Here, we show that in colitic mice, the tolerogenic properties of CD103 1 MLN DC are lost and that this APC population now drives inflammatory T-cell responses that may c...

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“…As a result, these DCs become conditioned and initiate appropriate responses upon contact with commensal microbiota, such as the differentiation of Treg, Th2 and IgA-secreting B-cells (12) (Fig. 1).…”

Section: Toll-like Receptors Probiotics and Immunotolerancementioning

confidence: 99%

Role of Toll-like receptors in the development of immunotolerance mediated by probiotics

2010

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Commensal bacteria are important in intestinal homeostasis and appear to play a role in early tolerance to foreign antigens. The requirement for homeostatic balance between tolerance and immunity poses a unique regulatory challenge to mucosal immune systems. Dysregulation of this balance can contribute to the pathogenesis of numerous inflammatory conditions such as inflammatory bowel diseases. The primary response to these bacteria is triggered by pattern recognition receptors (PRR), which bind pathogen-associated molecular patterns (PAMP). PRR comprise Toll-like receptors (TLR), nucleotide-binding oligomerization domains, adhesion molecules and lectins. Probiotics are living commensal micro-organisms of the intestinal tract with clinically documented health effects in human subjects. They are known to affect the gastrointestinal tract and the associated immune system and to have numerous effects on intestinal function and immune responses, including immunotolerance. This last effect appears to be mediated via regulatory T-cell activation by intestinal dendritic cells and the low activation of T-helper 1 and 2 (Th1 and Th2) cell inflammatory responses. However, the precise mechanisms of probiotic activity remain poorly understood. The aim of the present work was to review the function of TLR in the development of immunotolerance and examine the specific role of probiotics in the regulation of tolerance to antigens.

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Dendritic cells in intestinal immune regulation

Cited by 678 publications

References 117 publications

From skin dendritic cells to a simplified classification of human and mouse dendritic cell subsets

From skin dendritic cells to a simplified classification of human and mouse dendritic cell subsets

Intestinal inflammation abrogates the tolerogenic properties of MLN CD103⁺ dendritic cells

Role of Toll-like receptors in the development of immunotolerance mediated by probiotics

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Dendritic cells in intestinal immune regulation

Cited by 678 publications

References 117 publications

From skin dendritic cells to a simplified classification of human and mouse dendritic cell subsets

From skin dendritic cells to a simplified classification of human and mouse dendritic cell subsets

Intestinal inflammation abrogates the tolerogenic properties of MLN CD103+ dendritic cells

Role of Toll-like receptors in the development of immunotolerance mediated by probiotics

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Intestinal inflammation abrogates the tolerogenic properties of MLN CD103⁺ dendritic cells