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Article ; Online: Pre-transplant donor specific antibodies in ABO incompatible kidney transplantation - data from the Swiss transplant cohort study.

Deng, Yun / Frischnknecht, Lukas / Wehmeier, Caroline / de Rougemont, Olivier / Villard, Jean / Ferrari-Lacraz, Sylvie / Golshayan, Déla / Gannagé, Monique / Binet, Isabelle / Wirthmueller, Urs / Sidler, Daniel / Schachtner, Thomas / Schaub, Stefan / Nilsson, Jakob

Frontiers in immunology

2024 Volume 15, Page(s) 1355128

Abstract: Background: Living donor (LD) kidney transplantation in the setting of ABO blood group incompatibility (ABOi) has been previously reported to be associated with increased risk for antibody-mediated rejection (ABMR). It is however unclear if the presence ...

Abstract	Background: Living donor (LD) kidney transplantation in the setting of ABO blood group incompatibility (ABOi) has been previously reported to be associated with increased risk for antibody-mediated rejection (ABMR). It is however unclear if the presence of pre-transplant donor specific antibodies (DSA) works as an additive risk factor in the setting of ABOi and if DSA positive ABOi transplants have a significantly worse long-term outcome as compared with ABO compatible (ABOc) DSA positive transplants. Methods: We investigated the effect of pre-transplant DSA in the ABOi and ABOc setting on the risk of antibody-mediated rejection (ABMR) and graft loss in a cohort of 952 LD kidney transplants. Results: We found a higher incidence of ABMR in ABOi transplants as compared to ABOc transplants but this did not significantly affect graft survival or overall survival which was similar in both groups. The presence of pre-transplant DSA was associated with a significantly increased risk of ABMR and graft loss both in the ABOi and ABOc setting. We could not detect an additional risk of DSA in the ABOi setting and outcomes were comparable between DSA positive ABOi and ABOc recipients. Furthermore, a combination of DSA directed at both Class I and Class II, as well as DSA with a high mean fluorescence intensity (MFI) showed the strongest relation to ABMR development and graft loss. Conclusion: The presence of pre-transplant DSA was associated with a significantly worse long-term outcome in both ABOi and ABOc LD kidney transplants and our results suggests that the risk associated with pre-transplant DSA is perhaps not augmented in the ABOi setting. Our study is the first to investigate the long-term effects of DSA in the ABOi setting and argues that pre-transplant DSA risk could potentially be evaluated similarly regardless of ABO compatibility status.
MeSH term(s)	Humans ; Kidney Transplantation/adverse effects ; Cohort Studies ; Switzerland/epidemiology ; Living Donors ; Graft Rejection ; ABO Blood-Group System ; Antibodies
Chemical Substances	ABO Blood-Group System ; Antibodies
Language	English
Publishing date	2024-02-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1355128
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Article ; Online: Donation type and the effect of pre-transplant donor specific antibodies - Data from the Swiss Transplant Cohort Study.

de Rougemont, Olivier / Deng, Yun / Frischknecht, Lukas / Wehmeier, Caroline / Villard, Jean / Ferrari-Lacraz, Sylvie / Golshayan, Déla / Gannagé, Monique / Binet, Isabelle / Wirthmueller, Urs / Sidler, Daniel / Schachtner, Thomas / Schaub, Stefan / Nilsson, Jakob

Frontiers in immunology

2023 Volume 14, Page(s) 1104371

Abstract: Introduction: The type of donation may affect how susceptible a donor kidney is to injury from pre-existing alloimmunity. Many centers are, therefore, reluctant to perform donor specific antibody (DSA) positive transplantations in the setting of ... ...

Abstract	Introduction: The type of donation may affect how susceptible a donor kidney is to injury from pre-existing alloimmunity. Many centers are, therefore, reluctant to perform donor specific antibody (DSA) positive transplantations in the setting of donation after circulatory death (DCD). There are, however, no large studies comparing the impact of pre-transplant DSA stratified on donation type in a cohort with a complete virtual cross-match and long-term follow-up of transplant outcome. Methods: We investigated the effect of pre-transplant DSA on the risk of rejection, graft loss, and the rate of eGFR decline in 1282 donation after brain death (DBD) transplants and compared it to 130 (DCD) and 803 living donor (LD) transplants. Results: There was a significant worse outcome associated with pre-transplant DSA in all of the studied donation types. DSA directed against Class II HLA antigens as well as a high cumulative mean fluorescent intensity (MFI) of the detected DSA showed the strongest association with worse transplant outcome. We could not detect a significant additive negative effect of DSA in DCD transplantations in our cohort. Conversely, DSA positive DCD transplants appeared to have a slightly better outcome, possibly in part due to the lower mean fluorescent intensity (MFI) of the pre-transplant DSA. Indeed when DCD transplants were compared to DBD transplants with similar MFI (<6.5k), graft survival was not significantly different. Discussion: Our results suggest that the negative impact of pre-transplant DSA on graft outcome could be similar between all donation types. This suggests that immunological risk assessment could be performed in a similar way regardless of the type of donor kidney transplantation.
MeSH term(s)	Humans ; Antibodies ; Blood Grouping and Crossmatching ; Cohort Studies ; Living Donors ; Switzerland
Chemical Substances	Antibodies
Language	English
Publishing date	2023-02-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1104371
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Article ; Online: Monitoring Antigen Processing for MHC Presentation via Macroautophagy.

Gannage, Monique / da Silva, Rosa Barreira / Münz, Christian

Methods in molecular biology (Clifton, N.J.)

2019 Volume 1988, Page(s) 357–373

Abstract: Macroautophagy has recently emerged as an important catabolic process involved not only in innate immunity but also in adaptive immunity. Initially described to deliver intracellular antigens to MHC class II loading compartments, its molecular machinery ... ...

Abstract	Macroautophagy has recently emerged as an important catabolic process involved not only in innate immunity but also in adaptive immunity. Initially described to deliver intracellular antigens to MHC class II loading compartments, its molecular machinery has now also been described to impact the delivery of extracellular antigens to MHC class II loading compartments through the noncanonical use of the macroautophagy machinery during LC3-associated phagocytosis (LAP). Therefore, in pathological situations (viral or bacterial infections, tumorigenesis) the pathway might be involved in shaping CD4
MeSH term(s)	A549 Cells ; Antigen Presentation/immunology ; Antigens, Neoplasm/metabolism ; Autophagosomes/metabolism ; CD4-Positive T-Lymphocytes/immunology ; Clone Cells ; Dendritic Cells/metabolism ; Green Fluorescent Proteins/metabolism ; HEK293 Cells ; Histocompatibility Antigens Class II/immunology ; Humans ; Immunologic Techniques/methods ; Interferon-gamma/metabolism ; Macroautophagy ; Membrane Proteins/metabolism ; Monocytes/cytology
Chemical Substances	Antigens, Neoplasm ; CTAG1B protein, human ; Histocompatibility Antigens Class II ; Membrane Proteins ; Green Fluorescent Proteins (147336-22-9) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2019-05-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-9450-2_25
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Article ; Online: ATGs help MHC class II, but inhibit MHC class I antigen presentation.

Loi, Monica / Gannagé, Monique / Münz, Christian

Autophagy

2016 Volume 12, Issue 9, Page(s) 1681–1682

Abstract: We have recently shown that the LC3/Atg8 lipidation machinery of macroautophagy is involved in the internalization of MHC class I molecules. Decreased internalization in the absence of ATG5 or ATG7 leads to MHC class I surface stabilization on dendritic ... ...

Abstract	We have recently shown that the LC3/Atg8 lipidation machinery of macroautophagy is involved in the internalization of MHC class I molecules. Decreased internalization in the absence of ATG5 or ATG7 leads to MHC class I surface stabilization on dendritic cells and macrophages, resulting in elevated CD8(+) T cell responses during viral infections and improved immune control. Here, we discuss how the autophagic machinery supports MHC class II restricted antigen presentation, while compromising MHC class I presentation via internalization and degradation.
MeSH term(s)	Animals ; Antigen Presentation/immunology ; Autophagy ; Autophagy-Related Protein 5/metabolism ; Autophagy-Related Protein 7/metabolism ; CD8-Positive T-Lymphocytes/cytology ; Cell Membrane/metabolism ; Cell-Free System ; Dendritic Cells/metabolism ; Histocompatibility Antigens Class II/metabolism ; Humans ; Macrophages/metabolism ; Phagocytosis ; T-Lymphocytes/immunology
Chemical Substances	ATG5 protein, human ; Autophagy-Related Protein 5 ; Histocompatibility Antigens Class II ; ATG7 protein, human (EC 6.2.1.45) ; Autophagy-Related Protein 7 (EC 6.2.1.45)
Language	English
Publishing date	2016-07-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.1080/15548627.2016.1203488
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Article ; Online: The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation - Data from the Swiss transplant cohort study.

Frischknecht, Lukas / Deng, Yun / Wehmeier, Caroline / de Rougemont, Olivier / Villard, Jean / Ferrari-Lacraz, Sylvie / Golshayan, Déla / Gannagé, Monique / Binet, Isabelle / Wirthmueller, Urs / Sidler, Daniel / Schachtner, Thomas / Schaub, Stefan / Nilsson, Jakob

Frontiers in immunology

2022 Volume 13, Page(s) 1005790

Abstract: Background: Pre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean ... ...

Abstract	Background: Pre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM). Methods: We investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls. Results: Pre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR. Conclusion: Our results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA.
MeSH term(s)	Antibodies ; Cohort Studies ; Graft Rejection ; Graft Survival ; HLA Antigens ; HLA-DP Antigens ; Humans ; Kidney Transplantation/adverse effects ; Switzerland ; Tissue Donors
Chemical Substances	Antibodies ; HLA Antigens ; HLA-DP Antigens
Language	English
Publishing date	2022-09-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1005790
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Article ; Online: Endocytosis regulation by autophagy proteins in MHC restricted antigen presentation.

Keller, Christian W / Loi, Monica / Ligeon, Laure-Anne / Gannagé, Monique / Lünemann, Jan D / Münz, Christian

Current opinion in immunology

2018 Volume 52, Page(s) 68–73

Abstract: The macroautophagy machinery supports membrane remodeling and fusion events that lead to the engulfment of cytoplasmic constituents in autophagosomes and their degradation in lysosomes. The capacity of this machinery to regulate membrane adaptors and ... ...

Abstract	The macroautophagy machinery supports membrane remodeling and fusion events that lead to the engulfment of cytoplasmic constituents in autophagosomes and their degradation in lysosomes. The capacity of this machinery to regulate membrane adaptors and influence vesicle fusion with lysosomes seems to be used not only for autophagosomes, but also for endosomes. We summarize recent evidence that two aspects of endocytosis are regulated by parts of the macroautophagy machinery. These are recruitment of adaptors for the internalization of surface receptors and the fusion of phagosomes with lysosomes. Antigen processing for MHC presentation is affected by these alternative functions of the macroautophagy machinery. Primarily extracellular antigen presentation by MHC class II molecules after phagocytosis benefits from this regulation of phagosome maturation. Furthermore, MHC class I molecules are more efficiently internalized in the presence of the core macroautophagy machinery. The identification of these alternative functions of macroautophagy proteins not only complicates the interpretation of their deficiencies in biological processes, but could also be harnessed for the regulation of antigen presentation to T cells.
MeSH term(s)	Animals ; Antigen Presentation/immunology ; Antigens/immunology ; Antigens/metabolism ; Autophagy/genetics ; Autophagy/immunology ; Autophagy-Related Proteins/genetics ; Autophagy-Related Proteins/metabolism ; Endocytosis/immunology ; Histocompatibility Antigens/immunology ; Histocompatibility Antigens/metabolism ; Humans ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; Phagocytes/immunology ; Phagocytes/metabolism ; Phagocytosis/genetics ; Phagocytosis/immunology ; Phagosomes/immunology ; Phagosomes/metabolism
Chemical Substances	Antigens ; Autophagy-Related Proteins ; Histocompatibility Antigens ; MAP1LC3A protein, human ; Microtubule-Associated Proteins
Language	English
Publishing date	2018-04-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2018.04.014
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Article ; Online: The Tumor Antigen NY-ESO-1 Mediates Direct Recognition of Melanoma Cells by CD4+ T Cells after Intercellular Antigen Transfer.

Fonteneau, Jean Francois / Brilot, Fabienne / Münz, Christian / Gannagé, Monique

Journal of immunology (Baltimore, Md. : 1950)

2016 Volume 196, Issue 1, Page(s) 64–71

Abstract: NY-ESO-1-specific CD4(+) T cells are of interest for immune therapy against tumors, because it has been shown that their transfer into a patient with melanoma resulted in tumor regression. Therefore, we investigated how NY-ESO-1 is processed onto MHC ... ...

Abstract	NY-ESO-1-specific CD4(+) T cells are of interest for immune therapy against tumors, because it has been shown that their transfer into a patient with melanoma resulted in tumor regression. Therefore, we investigated how NY-ESO-1 is processed onto MHC class II molecules for direct CD4(+) T cell recognition of melanoma cells. We could rule out proteasome and autophagy-dependent endogenous Ag processing for MHC class II presentation. In contrast, intercellular Ag transfer, followed by classical MHC class II Ag processing via endocytosis, sensitized neighboring melanoma cells for CD4(+) T cell recognition. However, macroautophagy targeting of NY-ESO-1 enhanced MHC class II presentation. Therefore, both elevated NY-ESO-1 release and macroautophagy targeting could improve melanoma cell recognition by CD4(+) T cells and should be explored during immunotherapy of melanoma.
MeSH term(s)	Acetylcysteine/analogs & derivatives ; Acetylcysteine/pharmacology ; Antigen Presentation/immunology ; Antigens, Neoplasm/immunology ; Autophagy/immunology ; Autophagy-Related Protein 12 ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/transplantation ; Cell Line, Tumor ; Chloroquine/pharmacology ; Dendritic Cells/immunology ; Endocytosis/immunology ; Epitopes, T-Lymphocyte/immunology ; Histocompatibility Antigens Class II/immunology ; Humans ; Immunotherapy, Adoptive ; Leupeptins ; Lymphocyte Activation/immunology ; Lysosomal-Associated Membrane Protein 2/genetics ; Melanoma/immunology ; Melanoma/therapy ; Membrane Proteins/immunology ; RNA Interference ; RNA, Small Interfering ; Small Ubiquitin-Related Modifier Proteins/genetics
Chemical Substances	ATG12 protein, human ; Antigens, Neoplasm ; Autophagy-Related Protein 12 ; CTAG1B protein, human ; Epitopes, T-Lymphocyte ; Histocompatibility Antigens Class II ; LAMP2 protein, human ; Leupeptins ; Lysosomal-Associated Membrane Protein 2 ; Membrane Proteins ; RNA, Small Interfering ; Small Ubiquitin-Related Modifier Proteins ; lactacystin (133343-34-7) ; Chloroquine (886U3H6UFF) ; benzyloxycarbonylleucyl-leucyl-leucine aldehyde (RF1P63GW3K) ; Acetylcysteine (WYQ7N0BPYC)
Language	English
Publishing date	2016-01-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1402664
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Article ; Online: Macroautophagy in lymphatic endothelial cells inhibits T cell-mediated autoimmunity.

Harlé, Guillaume / Kowalski, Camille / Dubrot, Juan / Brighouse, Dale / Clavel, Gaëlle / Pick, Robert / Bessis, Natacha / Niven, Jennifer / Scheiermann, Christoph / Gannagé, Monique / Hugues, Stéphanie

The Journal of experimental medicine

2021 Volume 218, Issue 6

Abstract: Lymphatic endothelial cells (LECs) present peripheral tissue antigens to induce T cell tolerance. In addition, LECs are the main source of sphingosine-1-phosphate (S1P), promoting naive T cell survival and effector T cell exit from lymph nodes (LNs). ... ...

Abstract	Lymphatic endothelial cells (LECs) present peripheral tissue antigens to induce T cell tolerance. In addition, LECs are the main source of sphingosine-1-phosphate (S1P), promoting naive T cell survival and effector T cell exit from lymph nodes (LNs). Autophagy is a physiological process essential for cellular homeostasis. We investigated whether autophagy in LECs modulates T cell activation in experimental arthritis. Whereas genetic abrogation of autophagy in LECs does not alter immune homeostasis, it induces alterations of the regulatory T cell (T reg cell) population in LNs from arthritic mice, which might be linked to MHCII-mediated antigen presentation by LECs. Furthermore, inflammation-induced autophagy in LECs promotes the degradation of Sphingosine kinase 1 (SphK1), resulting in decreased S1P production. Consequently, in arthritic mice lacking autophagy in LECs, pathogenic Th17 cell migration toward LEC-derived S1P gradients and egress from LNs are enhanced, as well as infiltration of inflamed joints, resulting in exacerbated arthritis. Our results highlight the autophagy pathway as an important regulator of LEC immunomodulatory functions in inflammatory conditions.
MeSH term(s)	Animals ; Arthritis/immunology ; Autoimmunity/immunology ; Cell Movement/immunology ; Cells, Cultured ; Endothelial Cells/immunology ; Humans ; Immune Tolerance/immunology ; Inflammation/immunology ; Lymph Nodes/immunology ; Lymphatic Vessels/immunology ; Lysophospholipids/immunology ; Macroautophagy/immunology ; Mice ; Mice, Inbred C57BL ; Sphingosine/analogs & derivatives ; Sphingosine/immunology ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology
Chemical Substances	Lysophospholipids ; sphingosine 1-phosphate (26993-30-6) ; Sphingosine (NGZ37HRE42)
Language	English
Publishing date	2021-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20201776
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Article ; Online: Macroautophagy in Dendritic Cells Controls the Homeostasis and Stability of Regulatory T Cells.

Niven, Jennifer / Madelon, Natacha / Page, Nicolas / Caruso, Assunta / Harlé, Guillaume / Lemeille, Sylvain / Seemayer, Christian A / Hugues, Stéphanie / Gannagé, Monique

Cell reports

2019 Volume 28, Issue 1, Page(s) 21–29.e6

Abstract: Regulatory T cells (Tregs) play a crucial role in controlling autoimmune and inflammatory responses. Recent studies have demonstrated that dendritic cells (DCs) contribute to the homeostasis of peripheral Tregs. Autophagy, a critical pathway for cellular ...

Abstract	Regulatory T cells (Tregs) play a crucial role in controlling autoimmune and inflammatory responses. Recent studies have demonstrated that dendritic cells (DCs) contribute to the homeostasis of peripheral Tregs. Autophagy, a critical pathway for cellular homeostasis, is active in DCs and is upregulated in different inflammatory conditions. We have shown that Tregs are expanded and have phenotypic alterations and impaired suppressive functions in mice with autophagy-deficient DCs. RNA profiling of Tregs revealed that autophagy in DCs is required to stabilize Treg expression signatures. This phenotype is linked to the downregulation of ICOS-Ligand expression in autophagy-deficient DCs, a consequence of the accumulation of ADAM10, the metalloproteinase responsible for its cleavage. Upon inflammation, in antigen-induced arthritis, mice with autophagy-deficient DCs exhibit increased synovial inflammation and cartilage and bone erosion correlating with Treg-to-Th17 conversion. Our data reveal a mechanism that couples autophagy deficiency in DCs to the function, homeostasis, and stability of Tregs.
MeSH term(s)	Animals ; Autophagy-Related Protein 5/genetics ; Autophagy-Related Protein 5/metabolism ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Homeostasis/immunology ; Inducible T-Cell Co-Stimulator Ligand/genetics ; Inducible T-Cell Co-Stimulator Ligand/metabolism ; Inflammation/genetics ; Inflammation/immunology ; Macroautophagy/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Th17 Cells/immunology
Chemical Substances	Atg5 protein, mouse ; Autophagy-Related Protein 5 ; Forkhead Transcription Factors ; Foxp3 protein, mouse ; Icosl protein, mouse ; Inducible T-Cell Co-Stimulator Ligand
Language	English
Publishing date	2019-07-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2019.05.110
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Article: Autophagy in MHC class II presentation of endogenous antigens.

Gannagé, Monique / Münz, Christian

Current topics in microbiology and immunology

2009 Volume 335, Page(s) 123–140

Abstract: Macroautophagy is a catabolic process for the lysosomal turnover of cell organelles and protein aggregates. Lysosomal degradation products are displayed by major histocompatibility class II molecules to CD4(+) T cells in the steady state for tolerance ... ...

Abstract	Macroautophagy is a catabolic process for the lysosomal turnover of cell organelles and protein aggregates. Lysosomal degradation products are displayed by major histocompatibility class II molecules to CD4(+) T cells in the steady state for tolerance induction and during infections to mount adaptive immune responses. It has recently been shown that macroautophagy substrates can also give rise to MHC class II ligands. We review here the breadth of antigens that may utilize this pathway and the possible implications of this alternate route to MHC class II antigen presentation for immunity and tolerance. Based on this discussion, it is apparent that the regulation of macroautophagy may be beneficial in various disease settings in order to enhance adaptive immune responses or to reduce autoimmunity.
MeSH term(s)	Adaptive Immunity ; Animals ; Antigen Presentation ; Autophagy/immunology ; CD4-Positive T-Lymphocytes/immunology ; Histocompatibility Antigens Class II/immunology ; Humans
Chemical Substances	Histocompatibility Antigens Class II
Language	English
Publishing date	2009
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	0070-217X
ISSN	0070-217X
DOI	10.1007/978-3-642-00302-8_6
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