Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen

Akbari, Omid; DeKruyff, Rosemarie H.; Umetsu, Dale T.

doi:10.1038/90667

Cited by 1,102 publications

(913 citation statements)

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“…It was reported that pulmonary DCs from tolerized mice expressing IL-10 drive the generation of a population of IL-10-producing Tregs that Altering dendritic cell function to prevent asthma C-Y Hsu et al can inhibit subsequent responses to antigenic challenge. 26 Thus, induction of antigen-specific Tregs targeted to allergies and asthma is considered a promising immunomodulatory strategy to suppress the Th2 response.…”

Section: Discussionmentioning

confidence: 99%

Cytokine gene-modulated dendritic cells protect against allergic airway inflammation by inducing IL-10+IFN-γ+CD4+ T cells

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Cytokine gene-modulated dendritic cells protect against allergic airway inflammation by inducing IL-10+IFN-γ+CD4+ T cells

et al. 2010

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“…As a paradigm shift in the field of allergy, it has been shown that CD11c DC of the mucosal tissue are capable to induce effective tolerance to inhaled allergens, which reach the lung. This has been found to be mainly regulated by the DC-driven production of IL-10 and the co-stimulation of T-cells via Inducible-costimulatorLigand (ICOS-L), which leads to the induction of regulatory T-cells (TR 1 ) with a high production of the anti-inflammatory, tolerogenic mediator IL-10 and -at the end -the effective suppression of the allergic immune response (58,59).…”

Section: Antigen Presenting Cells Of the Lower Respiratory Tractmentioning

confidence: 99%

The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies

Novak

Allam

Betten

et al. 2003

Allergy

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It has been repeatedly demonstrated that allergic reactions are driven by the continuous flow of antigen uptake and presentation processes, which are perpetuated mainly by dendritic cells (DC). The ability of allergens to cause allergic inflammation is contingent upon the presence of an immunological milieu and microenvironment that either privileges Th2 responses or prohibits these reactions by the induction of contraregulatory anti‐inflammatory activities of the immune system. In the light of recent developments it appears that DC have to manage two opposing tasks: on the one hand they can favor pro‐inflammatory reactions and actively induce a T‐cell response, yet on the other hand they serve an important function as ‘silencers’ in the immune system by sending out anti‐inflammatory, tolerance inducing signals. This unique capacity of DC has opened several exciting possibilities for a role of DC in both – accelerating and slowing down allergic reactions. It is therefore a challenge to understand in which way DC subtypes located at distinct anatomic sites with frequent allergen exposure, such as the skin, the nasal mucosa, the respiratory tree or the mucosa of the intestinal tract can have an impact on mechanisms involved in tolerance induction or effective immunity.

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“…Treg and NKT cells have been shown to be associated with the control of lung inflammation. In addition, pulmonary DC have been found to produce IL-10 and mediate tolerance induced by respiratory exposure to antigen [14]; however, to the best of our knowledge, there is no report about the role of pulmonary stromal cells as the major component of the lung microenvironment in tolerance induction and inflammation control. How regulatory cells such as Treg are induced and maintained in the lung needs to be fully investigated.…”

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confidence: 99%

Pulmonary stromal cells induce the generation of regulatory DC attenuating T‐cell‐mediated lung inflammation

Guo

et al. 2008

Eur J Immunol

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The tissue microenvironment may affect the development and function of immune cells such as DC. Whether and how the pulmonary stromal microenvironment can affect the development and function of lung DC need to be investigated. Regulatory DC (DCreg) can regulate T-cell response. We wondered whether such regulatory DC exist in the lung and what is the effect of the pulmonary stromal microenvironment on the generation of DCreg. Here we demonstrate that murine pulmonary stromal cells can drive immature DC, which are regarded as being widely distributed in the lung, to proliferate and differentiate into a distinct subset of DCreg, which express high levels of CD11b but low levels of MHC class II (I-A), CD11c, secrete high amounts of IL-10, NO and prostaglandin E 2 (PGE 2 ) and suppress T-cell proliferation. The natural counterpart of DCreg in the lung with similar phenotype and regulatory function has been identified. Pulmonary stroma-derived TGF-b is responsible for the differentiation of immature DC to DCreg, and DCreg-derived PGE2 contributes to their suppression of T-cell proliferation. Moreover, DCreg can induce the generation of CD4 1 CD25 1 Foxp3 1 Treg. Importantly, infusion with DCreg attenuates T-cell-mediated eosinophilic airway inflammation in vivo. Therefore, the pulmonary microenvironment may drive the generation of DCreg, thus contributing to the maintenance of immune homoeostasis and the control of inflammation in the lung.Key words: DC . Immune regulation . Lung inflammation . Treg . Stromal cells Introduction DC are the most potent APC in the immune system, with unique capacity to activate naïve T cells and to initiate immune responses [1]. Now, increasing evidence demonstrates that, depending on the maturation state or subsets, DC can induce tolerance or downregulate immune responses [2,3]. Immature DC (imDC) have been shown to be able to induce Treg and promote alloantigen-specific tolerance. Recently, several types of DC with negative regulatory functions, designated as regulatory DC (DCreg), have been reported [3][4][5]. Up to now, regulatory DCreg were generated by culturing imDC in the presence of immunosuppressive cytokines such as IL-10 and TGF-b or immunomodulatory drugs [4][5][6], which does not represent the in vivo physiologic conditions of DCreg in the organ microenvironment. More and more data show that the microenvironment in certain tissues has the ability to induce DC development [7][8][9][10] and also affects the function of DC; for example, DC in brain and kidney display regulatory functions but not T-cell-activating functions [11,12]. Our previous studies demonstrate that endothelial splenic stromal cells, which are used to mimic the in vivo splenic microenvironment, can promote the proliferation of mature DC (maDC) [7] and hematopoietic stem cells [8], driving them to Ã These authors contributed equally to this work. The lung is one of the organs connected with the outside environment of the organism and interfaces a vast quantity of environmental antigens, some of which are dan...

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Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen

Cited by 1,102 publications

References 44 publications

Cytokine gene-modulated dendritic cells protect against allergic airway inflammation by inducing IL-10+IFN-γ+CD4+ T cells

Cytokine gene-modulated dendritic cells protect against allergic airway inflammation by inducing IL-10+IFN-γ+CD4+ T cells

The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies

Pulmonary stromal cells induce the generation of regulatory DC attenuating T‐cell‐mediated lung inflammation

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