Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells

Rimoldi, Monica; Chieppa, Marcello; Salucci, Valentina; Avogadri, Francesca; Sonzogni, Angelica; Sampietro, Gianluca; Nespoli, Angelo; Viale, Giuseppe; Allavena, Paola; Rescigno, María

doi:10.1038/ni1192

Cited by 734 publications

(780 citation statements)

References 42 publications

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“…Together, the results by Monteleone et al [13] suggest that even though DC are exposed to bacteria in the gut, they either do not respond because they do not express TLR, or they respond in a non-inflammatory mode via an IL-10 mediated mechanism. This is in-line with human data showing that DC isolated from the colon are unable to produce IL-12, but produce IL-10 and do not drive inflammatory responses even to a potent pathogen (Salmonella typhimurium) [8]. In that case it was postulated that epithelial cell-derived factors, including thymic stromal lymphopoietin (TSLP), were responsible for the 'education' of mucosal noninflammatory DC [8,16].…”

supporting

confidence: 76%

“…This is in-line with human data showing that DC isolated from the colon are unable to produce IL-12, but produce IL-10 and do not drive inflammatory responses even to a potent pathogen (Salmonella typhimurium) [8]. In that case it was postulated that epithelial cell-derived factors, including thymic stromal lymphopoietin (TSLP), were responsible for the 'education' of mucosal noninflammatory DC [8,16].…”

supporting

confidence: 76%

“…Several reports have shown that DC isolated from the lamina propria (LP) of the small intestine or from MLN participate in maintaining gut immune homeostasis via the induction of noninflammatory or tolerogenic responses [3][4][5][6][7][8]; however, a recent report has challenged this view showing that murine LP CD11c hi cells can be FACS-separated into two subpopulations, based on the expression of CD11b, that display different immunological properties [9]. CD11c hi CD11b + cells induce the development of Th17 cells while CD11c hi CD11b -cells induce IL-10-producing T cells [9].…”

mentioning

confidence: 99%

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Lamina propria dendritic cells: For whom the bell TOLLs?

Rescigno

Matteoli

2008

Eur J Immunol

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One of the major tasks of the mucosal immune system is to discriminate between dangerous and harmless antigens that are encountered daily at mucosal sites. In the gastrointestinal tract, immune cells have to tolerate food antigens and commensal microbes but at the same time have to induce a prompt response against invasive pathogens, when needed. In this issue of the European Journal of Immunology, it is shown that intestinal dendritic cell (DC) populations can be distinguished based on the expression level of Toll‐like receptors (TLR) and on the response of these TLR to their microbial ligands. DC either do not express TLR or they express them but respond in a non‐inflammatory mode. In this commentary, these findings are discussed in the context of available knowledge on lamina propria DC.See accompanying article http://dx.doi.org/10.1002/eji.200737909

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supporting

confidence: 76%

supporting

confidence: 76%

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confidence: 99%

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Lamina propria dendritic cells: For whom the bell TOLLs?

Rescigno

Matteoli

2008

Eur J Immunol

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“…For example, intestinal epithelial cells inhibit production of IL-12 by DC via thymic stromal lymphopoeitin such that the Th1-type response is limited in the intestine [10]. Thus, the microenvironment of the intestine plays a key role in the regulation of DC functions for immune homeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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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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