Linked Life Data

21753149

Source:http://linkedlifedata.com/resource/pubmed/id/21753149

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-8-3
pubmed:abstractText
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autoimmune disease that is caused by mutations in the AIRE gene. Murine studies have linked AIRE to thymocyte selection and peripheral deletional tolerance, but the pathogenesis of the human disease remains unclear. In this study, we show that APECED patients have elevated IL-7 levels and a drastically decreased expression of IL-7R on CD8(+) T cells. This is associated with increased proliferation and a decreased expression of the negative TCR regulator CD5 in the CD45RO(-) subset. The CD45RO(-) cells also display oligoclonal expansions, decreased expression of the lymph node homing factors CCR7 and CD62L, and increased expression of perforin, consistent with the accumulation of highly differentiated effector cells. The CD45RO(-)CCR7(+)CD8(+) population of cells with markers characteristic of naive phenotype is also skewed, as shown by decreased expression of CD5 and increased expression of perforin. The putative CD31(+) recent thymic emigrant population is likewise affected. These data are consistent with IL-7 dysregulation inducing a decreased threshold of TCR signaling and self-antigen-driven proliferation, probably in synergy with the failed thymic selection. The resultant loss of CD8(+) T cell homeostasis is likely to play a significant role in the pathogenesis of APECED. Our findings may also hold lessons for other diseases in which the IL-7-IL-7R pathway has emerged as a risk factor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
187
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2023-30
pubmed:meshHeading
pubmed-meshheading:21753149-Adult, pubmed-meshheading:21753149-Animals, pubmed-meshheading:21753149-Antigens, Differentiation, pubmed-meshheading:21753149-CD8-Positive T-Lymphocytes, pubmed-meshheading:21753149-Child, pubmed-meshheading:21753149-Child, Preschool, pubmed-meshheading:21753149-Female, pubmed-meshheading:21753149-Gene Expression Regulation, pubmed-meshheading:21753149-Homeostasis, pubmed-meshheading:21753149-Humans, pubmed-meshheading:21753149-Interleukin-7, pubmed-meshheading:21753149-Male, pubmed-meshheading:21753149-Mice, pubmed-meshheading:21753149-Middle Aged, pubmed-meshheading:21753149-Polyendocrinopathies, Autoimmune, pubmed-meshheading:21753149-Receptors, Antigen, T-Cell, pubmed-meshheading:21753149-Receptors, Interleukin-7, pubmed-meshheading:21753149-Thymus Gland, pubmed-meshheading:21753149-Transcription Factors
pubmed:year
2011
pubmed:articleTitle
IL-7 dysregulation and loss of CD8+ T cell homeostasis in the monogenic human disease autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.
pubmed:affiliation
Department of Immunology, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, Non-U.S. Gov't