| 1. |
- Le Guen, Yann, et al.
(författare)
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Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
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Tidskriftsartikel (refereegranskat)abstract
- Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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| 2. |
- Arulampalam, V, et al.
(författare)
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The long and winding road to gut homeostasis
- 2006
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Ingår i: Current opinion in gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0267-1379. ; 22:4, s. 349-353
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Greicius, G, et al.
(författare)
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A CLA's act: feeding away inflammation
- 2004
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 127:3, s. 994-996
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
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| 8. |
- Greicius, G, et al.
(författare)
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CEACAM1 is a potent regulator of B cell receptor complex-induced activation
- 2003
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Ingår i: Journal of leukocyte biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 74:1, s. 126-134
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Tidskriftsartikel (refereegranskat)abstract
- Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CD66a) is a member of the immunoglobulin (Ig) superfamily, previously characterized as an adhesion and signaling molecule in epithelial, endothelial, and hematopoietic cells. Here, we show that the CEACAM1 isoform expression pattern is different in nonactivated and activated primary mouse B lymphocytes and that CEACAM1 influences B cell receptor complex-mediated activation. A CEACAM1-specific monoclonal antibody strongly triggered proliferation of mouse B cells when combined with surface IgM cross-linking. However, anti-CEACAM1 was not mitogenic when added alone. The proliferation was more pronounced and lasted longer as compared with other activators of B cells, such as anti-IgM in the presence of interleukin-4 or lipopolysaccharide. A similar, costimulatory effect was exerted by CEACAM1-expressing fibroblasts, indicating that homophilic CEACAM1–CEACAM1 cell-mediated binding is the physiological stimulus for CEACAM1-triggered B cell signaling. The anti-CEACAM1/anti-IgM-activated cells aggregated in a lymphocyte function-associated antigen-1-dependent manner. Furthermore, cells that were activated by anti-CEACAM1/anti-IgM secreted Ig but did not go through Ig class-switching. Anti-CEACAM1 induced phosphorylation of c-Jun N-terminal kinase (stress-activated protein kinase) but did not activate the extracellular signal-regulated kinase or p38 mitogen-activated protein kinases.
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