IL-1 breaks tolerance through expansion of CD25+ effector T cells

O'Sullivan, B.J., Thomas, H.E., Pai, S., Santamaria, P., Iwakura, Y., Steptoe, R.J., Kay, T.W.H., and Thomas, R. (2006) IL-1 breaks tolerance through expansion of CD25+ effector T cells. The Journal of Immunology, 176 (12). pp. 7278-7287.

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Abstract

IL-1 is a key proinflammatory driver of several autoimmune diseases including juvenile inflammatory arthritis, diseases with mutations in the NALP/cryopyrin complex and Crohn’s disease, and is genetically or clinically associated with many others. IL-1 is a pleiotropic proinflammatory cytokine; however the mechanisms by which increased IL-1 signaling promotes autoreactive T cell activity are not clear. Here we show that autoimmune-prone NOD and IL-1 receptor antagonist-deficient C57BL/6 mice both produce high levels of IL-1, which drives autoreactive effector cell expansion. IL-1β drives proliferation and cytokine production by CD4+CD25+FoxP3− effector/memory T cells, attenuates CD4+CD25+FoxP3+ regulatory T cell function, and allows escape of CD4+CD25− autoreactive effectors from suppression. Thus, inflammation or constitutive overexpression of IL-1β in a genetically predisposed host can promote autoreactive effector T cell expansion and function, which attenuates the ability of regulatory T cells to maintain tolerance to self.

Item ID: 49536
Item Type: Article (Refereed Research - C1)
ISSN: 1550-6606
Date Deposited: 11 Jul 2017 01:46
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060111 Signal Transduction @ 34%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 33%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 33%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 33%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 33%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920104 Diabetes @ 34%
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