The autoimmune regulator (Aire) controls iNKT cell development and maturation

Mi, Qing Sheng; Deng, Zhong; Joshi, Sunil; Wang, Zai Zhao; Zhou, Li; Eckenrode, Sarah; Joshi, Ratanmani; Ly, Dalam; Yu, Bing; Delovitch, Terry L.; She, Jin Xiong

doi:10.1038/nm1424

Cited by 7 publications

(1 citation statement)

References 15 publications

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“…Clearly, the potential for Aire to impact on regulatory T-cell subsets provides a credible explanation of the disease profile of Aire-deficient individuals and evidence that the development of Treg is largely unaffected only highlights the need to examine NKT cells in Aire-deficient mice [18]. Speculation of a defect within the NKT cell compartment led to a recent study that reported a severe NKT cell deficiency in Aire-deficient mice [30]; however, the article was later retracted [31] and the issue remains unresolved. We have directly addressed the question by characterizing the size, composition and function of the thymic and peripheral NKT cell compartments of Aire-deficient mice.…”

Section: Introductionmentioning

confidence: 99%

NKT cell development in the absence of the autoimmune regulator gene (Aire)

et al. 2008

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Autoimmune regulator gene (Aire)-deficient mice develop an array of autoimmune lesions that reflect failures of immune tolerance. Negative selection is clearly compromised in these mice, but there is evidence to suggest that other mechanisms of tolerance might also be affected, including a possible impairment of regulatory T cell (Treg) development. Studies to date have failed to demonstrate any significant impact on the development or function of the FOXP3 1 Treg compartment, but NKT cells represent a distinct regulatory cell lineage that also develop in the thymus and which are known to influence selftolerance. Aire-related defects coincide with NKT cell deficiencies in a number of animal models, but the direct consequence of Aire-deficiency on NKT cell development has not been established. In this study, we demonstrate that the frequency, distribution and cytokine production of NKT cells and their subsets is principally normal in Aire-deficient mice. We conclude that Aire has little or no effect on regulatory T cell development in general and NKT cells in particular.

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Section: Introductionmentioning

confidence: 99%

NKT cell development in the absence of the autoimmune regulator gene (Aire)

et al. 2008

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Candida

Lilić

Haynes

Immunology of Fungal Infections

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Experimental models of spontaneous autoimmune disease in the central nervous system

2007

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Animal models have become essential tools for studying the human autoimmune disease. They are of vital importance in explorations of disease aspects, where, for diverse reasons, human material is unavailable. This is especially true for disease processes preceding clinical diagnosis and for tissues, which are inaccessible to routine biopsy. Early developing multiple sclerosis (MS) makes an excellent point in case for these limitations. Useful disease models should be developing spontaneously, without a need of artificial, adjuvant-supported induction protocols, and they should reflect credibly at least some of the complex features of human disease. The aim of this review is to compile models that exhibit spontaneous organ-specific autoimmunity and explore their use for studying MS. We first evaluate a few naturally occurring models of organ-specific autoimmune diseases and then screen autoimmunity in animals with compromised immune regulation (neonatal thymectomy, transgenesis, etc.). While most of these models affect organs other than the nervous tissues, central nervous system (CNS)-specific autoimmune disease is readily noted either after transgenic overexpression of cytokines or chemokines within the CNS or by introducing CNS-specific immune receptors into the lymphocyte repertoire. Most recently, spontaneous autoimmunity resembling MS was obtained by transgenic expression of self-reactive T cell receptors and B cell receptors. These transgenic models are not only of promise for studying directly disease processes during the entire course of the disease but may also be helpful in drug discovery.

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The autoimmune regulator (Aire) controls iNKT cell development and maturation

Cited by 7 publications

References 15 publications

NKT cell development in the absence of the autoimmune regulator gene (Aire)

NKT cell development in the absence of the autoimmune regulator gene (Aire)

Candida

Experimental models of spontaneous autoimmune disease in the central nervous system

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