Basic science for the clinician 37: Protecting against autoimmunity-tolerance: mechanisms of negative selection in the thymus.

Basic science for the clinician 37: Protecting against autoimmunity-tolerance: mechanisms of negative selection in the thymus. Research Abstract Details 

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Basic science for the clinician 37: Protecting against autoimmunity-tolerance: mechanisms of negative selection in the thymus. Abstract Text:

As noted in previous articles in this series, tolerance, the ability of the immune system to differentiate self from nonself and leave the former alone, is a vital characteristic of a successful (and safe) immune system. With the detection of the molecule called aire (autoimmune regulator), the mechanism whereby autoreactive thymocytes encounter extrathymic proteins within the thymus and therefore are deleted, is now far better understood; aire was the subject of a prior article in this series. The absence of aire leads to autoimmune polyendocrinopathy, proof that aire is the center of an amazing "filtering" system. However, there are other mechanisms at work. Irregularities in expression of other proteins such as hypoxia-induced factor-1 (HIF-1) and CTLA4, have been implicated in autoimmune disease, the former in rheumatoid arthritis, the latter in autoimmune thyroid disease and lupus. Defects in intracellular factors involved in transcription of key apoptotic proteins have also been implicated in the escape of autoreactive thymocytes from the thymus, leading to autoimmune and lymphoproliferative syndromes as well. Changes in the proteins that oversee acetylation of histone lead to differential patterns of gene expression. At least 2 proteins involved in this process, HDAC and nur77, have been implicated in changes in survival of thymocytes. Yet again, there are multiple layers at work in the immune system; I have no idea how many more will be brought to light, which are phylogenetically most ancient or which will prove the most clinically relevant. For now, it is enough to bask in our new-found knowledge and know that the time from laboratory oddity, to animal model development, to therapeutic and/or diagnostic applications grows shorter each year since the molecular biologic revolution.

Basic science for the clinician 37: Protecting against autoimmunity-tolerance: mechanisms of negative selection in the thymus. Publishing Authors By Initials

For similar proteins: transcription factors research abstracts see: proteins: transcription factors research

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Basic science for the clinician 37: Protecting against autoimmunity-tolerance: mechanisms of negative selection in the thymus. Journal Published:

PUBLICATION TYPE: Review

Journal: Journal of clinical rheumatology : practical repor

VOLUME: 12

Page Numbers: 99-101

Journal Abbreviation: J Clin Rheumatol

ISSN: 1076-1608

DAY: 10

MONTH: Apr

YEAR: 2006

Basic science for the clinician 37: Protecting against autoimmunity-tolerance: mechanisms of negative selection in the thymus. Information

Number of References: 12

LANGUAGE: eng

NlmUniqueID: 9518034

Basic science for the clinician 37: Protecting against autoimmunity-tolerance: mechanisms of negative selection in the thymus. Keywords Mesh Terms:

KEYWORDS: Transcription Factors

MESH TERMS: immunology

Chemical & Substance for Abstract: Basic science for the clinician 37: Protecting against autoimmunity-tolerance: mechanisms of negative selection in the thymus. Information

Substance Name: Histone Deacetylases

Registry Number: EC 3.5.1.-

Grant and Affiliation Information for Basic science for the clinician 37: Protecting against autoimmunity-tolerance: mechanisms of negative selection in the thymus.

AFFILIATION: Pharmaceutical Research Institute, Bristol-Myers Squibb, J.3100, PO Box 4000, Princeton, NJ 08543-4000, USA. leonard.sigal@bms.com

Country: United States

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MEDLINETA: J Clin Rheumatol

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