Active uptake of dendritic cell-derived exovesicles by epithelial cells induces the release of inflammatory mediators through a TNF-alpha-mediated pathway

Dendritic cells (DCs) can release hundreds of membrane vesicles, called exovesicles, which are able to activate resting DCs and distribute antigen. Here, we examined the role of mature DC-derived exovesicles in innate and adaptive immunity, in particular their capacity to activate epithelial cells....

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Published in:	The American journal of pathology Vol. 175; no. 2; p. 696
Main Authors:	Obregon, Carolina, Rothen-Rutishauser, Barbara, Gerber, Peter, Gehr, Peter, Nicod, Laurent P
Format:	Journal Article
Language:	English
Published:	United States 01.08.2009
Subjects:	Antigens, CD - metabolism CD40 Antigens - metabolism CD83 Antigen Dendritic Cells - immunology Dendritic Cells - metabolism Endocytosis - immunology Epithelial Cells - immunology Exosomes - metabolism Histocompatibility Antigens Class II - metabolism Humans Immunoglobulins - metabolism Inflammation Mediators - metabolism Membrane Glycoproteins - metabolism Tumor Necrosis Factor-alpha - metabolism
ISSN:	1525-2191, 1525-2191
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Abstract	Dendritic cells (DCs) can release hundreds of membrane vesicles, called exovesicles, which are able to activate resting DCs and distribute antigen. Here, we examined the role of mature DC-derived exovesicles in innate and adaptive immunity, in particular their capacity to activate epithelial cells. Our analysis of exovesicle contents showed that exovesicles contain major histocompatibility complex-II, CD40, and CD83 molecules in addition to tumor necrosis factor (TNF) receptors, TNFRI and TNFRII, and are important carriers of TNF-alpha. These exovesicles are rapidly internalized by epithelial cells, inducing the release of cytokines and chemokines, but do not transfer an alloantigen-presenting capacity to epithelial cells. Part of this activation appears to involve the TNF-alpha-mediated pathway, highlighting the key role of DC-derived exovesicles, not only in adaptive immunity, but also in innate immunity by triggering innate immune responses and activating neighboring epithelial cells to release cytokines and chemokines, thereby amplifying the magnitude of the innate immune response.
AbstractList	Dendritic cells (DCs) can release hundreds of membrane vesicles, called exovesicles, which are able to activate resting DCs and distribute antigen. Here, we examined the role of mature DC-derived exovesicles in innate and adaptive immunity, in particular their capacity to activate epithelial cells. Our analysis of exovesicle contents showed that exovesicles contain major histocompatibility complex-II, CD40, and CD83 molecules in addition to tumor necrosis factor (TNF) receptors, TNFRI and TNFRII, and are important carriers of TNF-alpha. These exovesicles are rapidly internalized by epithelial cells, inducing the release of cytokines and chemokines, but do not transfer an alloantigen-presenting capacity to epithelial cells. Part of this activation appears to involve the TNF-alpha-mediated pathway, highlighting the key role of DC-derived exovesicles, not only in adaptive immunity, but also in innate immunity by triggering innate immune responses and activating neighboring epithelial cells to release cytokines and chemokines, thereby amplifying the magnitude of the innate immune response.Dendritic cells (DCs) can release hundreds of membrane vesicles, called exovesicles, which are able to activate resting DCs and distribute antigen. Here, we examined the role of mature DC-derived exovesicles in innate and adaptive immunity, in particular their capacity to activate epithelial cells. Our analysis of exovesicle contents showed that exovesicles contain major histocompatibility complex-II, CD40, and CD83 molecules in addition to tumor necrosis factor (TNF) receptors, TNFRI and TNFRII, and are important carriers of TNF-alpha. These exovesicles are rapidly internalized by epithelial cells, inducing the release of cytokines and chemokines, but do not transfer an alloantigen-presenting capacity to epithelial cells. Part of this activation appears to involve the TNF-alpha-mediated pathway, highlighting the key role of DC-derived exovesicles, not only in adaptive immunity, but also in innate immunity by triggering innate immune responses and activating neighboring epithelial cells to release cytokines and chemokines, thereby amplifying the magnitude of the innate immune response. Dendritic cells (DCs) can release hundreds of membrane vesicles, called exovesicles, which are able to activate resting DCs and distribute antigen. Here, we examined the role of mature DC-derived exovesicles in innate and adaptive immunity, in particular their capacity to activate epithelial cells. Our analysis of exovesicle contents showed that exovesicles contain major histocompatibility complex-II, CD40, and CD83 molecules in addition to tumor necrosis factor (TNF) receptors, TNFRI and TNFRII, and are important carriers of TNF-alpha. These exovesicles are rapidly internalized by epithelial cells, inducing the release of cytokines and chemokines, but do not transfer an alloantigen-presenting capacity to epithelial cells. Part of this activation appears to involve the TNF-alpha-mediated pathway, highlighting the key role of DC-derived exovesicles, not only in adaptive immunity, but also in innate immunity by triggering innate immune responses and activating neighboring epithelial cells to release cytokines and chemokines, thereby amplifying the magnitude of the innate immune response.
Author	Obregon, Carolina Rothen-Rutishauser, Barbara Nicod, Laurent P Gerber, Peter Gehr, Peter
Author_xml	– sequence: 1 givenname: Carolina surname: Obregon fullname: Obregon, Carolina organization: Médecin chef, Service de pneumologie, CHUV, 1011 Lausanne. Switzerland – sequence: 2 givenname: Barbara surname: Rothen-Rutishauser fullname: Rothen-Rutishauser, Barbara – sequence: 3 givenname: Peter surname: Gerber fullname: Gerber, Peter – sequence: 4 givenname: Peter surname: Gehr fullname: Gehr, Peter – sequence: 5 givenname: Laurent P surname: Nicod fullname: Nicod, Laurent P
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SubjectTerms	Antigens, CD - metabolism CD40 Antigens - metabolism CD83 Antigen Dendritic Cells - immunology Dendritic Cells - metabolism Endocytosis - immunology Epithelial Cells - immunology Exosomes - metabolism Histocompatibility Antigens Class II - metabolism Humans Immunoglobulins - metabolism Inflammation Mediators - metabolism Membrane Glycoproteins - metabolism Tumor Necrosis Factor-alpha - metabolism
Title	Active uptake of dendritic cell-derived exovesicles by epithelial cells induces the release of inflammatory mediators through a TNF-alpha-mediated pathway
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