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Allele Specific Expression of MICA Variants in Human Fibroblasts Suggests a Pathogenic Mechanism

The major histocompatibility complex class I chain-related gene A (MICA) is involved in immune responses of both nature killer (NK) cells and subsets of T cells with its receptor NKG2D. MICA is highly polymorphic in sequence which leads to MICA protein variants with distinct features. Specific polym...

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Detalles Bibliográficos
Autores principales: Shi, Chunhua, Li, Hongye, Couturier, Jacob P, Yang, Karen, Guo, Xinjian, He, Dongyi, Lewis, Dorothy E, Zhou, Xiaodong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Open 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550945/
https://www.ncbi.nlm.nih.gov/pubmed/26322142
http://dx.doi.org/10.2174/1874312901409010060
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author Shi, Chunhua
Li, Hongye
Couturier, Jacob P
Yang, Karen
Guo, Xinjian
He, Dongyi
Lewis, Dorothy E
Zhou, Xiaodong
author_facet Shi, Chunhua
Li, Hongye
Couturier, Jacob P
Yang, Karen
Guo, Xinjian
He, Dongyi
Lewis, Dorothy E
Zhou, Xiaodong
author_sort Shi, Chunhua
collection PubMed
description The major histocompatibility complex class I chain-related gene A (MICA) is involved in immune responses of both nature killer (NK) cells and subsets of T cells with its receptor NKG2D. MICA is highly polymorphic in sequence which leads to MICA protein variants with distinct features. Specific polymorphisms of MICA have been associated with inflammatory diseases, including ankylosing spondylitis (AS), ulcerative colitis (UC) and Behçet’s disease. Studies herein characterize expression features of three MICA variants including MICA*008, a common variant in general population, and *MICA*007 and *019, which are associated with susceptibility to inflammatory diseases. MICA*019 was highly expressed on the surface of fibroblasts whereas expression of MICA*007 was the lowest in the culture supernatant. MICA*008 had low cell surface expression but was the only MICA allele in which exosomal material was detected. Surface or membrane-bound MICA activates NKG2D-mediated cytotoxicity, whereas soluble and exosomal MICAs down-regulate NKG2D. Therefore, comparisons of these three MICA variants in fibroblasts provides insight into understanding how MICA associated immune responses could be regulated to influence levels of inflammation.
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spelling pubmed-45509452015-08-28 Allele Specific Expression of MICA Variants in Human Fibroblasts Suggests a Pathogenic Mechanism Shi, Chunhua Li, Hongye Couturier, Jacob P Yang, Karen Guo, Xinjian He, Dongyi Lewis, Dorothy E Zhou, Xiaodong Open Rheumatol J Article The major histocompatibility complex class I chain-related gene A (MICA) is involved in immune responses of both nature killer (NK) cells and subsets of T cells with its receptor NKG2D. MICA is highly polymorphic in sequence which leads to MICA protein variants with distinct features. Specific polymorphisms of MICA have been associated with inflammatory diseases, including ankylosing spondylitis (AS), ulcerative colitis (UC) and Behçet’s disease. Studies herein characterize expression features of three MICA variants including MICA*008, a common variant in general population, and *MICA*007 and *019, which are associated with susceptibility to inflammatory diseases. MICA*019 was highly expressed on the surface of fibroblasts whereas expression of MICA*007 was the lowest in the culture supernatant. MICA*008 had low cell surface expression but was the only MICA allele in which exosomal material was detected. Surface or membrane-bound MICA activates NKG2D-mediated cytotoxicity, whereas soluble and exosomal MICAs down-regulate NKG2D. Therefore, comparisons of these three MICA variants in fibroblasts provides insight into understanding how MICA associated immune responses could be regulated to influence levels of inflammation. Bentham Open 2015-08-26 /pmc/articles/PMC4550945/ /pubmed/26322142 http://dx.doi.org/10.2174/1874312901409010060 Text en © Shi et al.; Licensee Bentham Open. http://creativecommons.org/licenses/by-nc/3.0/ This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
spellingShingle Article
Shi, Chunhua
Li, Hongye
Couturier, Jacob P
Yang, Karen
Guo, Xinjian
He, Dongyi
Lewis, Dorothy E
Zhou, Xiaodong
Allele Specific Expression of MICA Variants in Human Fibroblasts Suggests a Pathogenic Mechanism
title Allele Specific Expression of MICA Variants in Human Fibroblasts Suggests a Pathogenic Mechanism
title_full Allele Specific Expression of MICA Variants in Human Fibroblasts Suggests a Pathogenic Mechanism
title_fullStr Allele Specific Expression of MICA Variants in Human Fibroblasts Suggests a Pathogenic Mechanism
title_full_unstemmed Allele Specific Expression of MICA Variants in Human Fibroblasts Suggests a Pathogenic Mechanism
title_short Allele Specific Expression of MICA Variants in Human Fibroblasts Suggests a Pathogenic Mechanism
title_sort allele specific expression of mica variants in human fibroblasts suggests a pathogenic mechanism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550945/
https://www.ncbi.nlm.nih.gov/pubmed/26322142
http://dx.doi.org/10.2174/1874312901409010060
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