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Type I Interferons Inhibition of Inflammatory T Helper Cell Responses in Systemic Lupus Erythematosus
Author(s) -
MANGINI ALYSON J.,
LAFYATIS ROBERT,
MAGUIRE VAN SEVENTER JEAN
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1422.002
Subject(s) - immunology , inflammation , immune system , autoimmune disease , systemic lupus erythematosus , biology , disease , medicine , antibody
: T helper (Th) cells play a central role in systemic lupus erythematosus (SLE). Activated autoreactive Th cells provide the help required for autoreactive B cells to differentiate and produce pathogenic autoAbs. Both autoAb‐containing immune complexes and direct effects of inflammatory Th cells promote tissue injury and organ damage. In SLE, triggering of plasmacytoid dendritic cell (pDC) Toll‐like receptors by autoimmune complexes containing nucleic acid autoantigens stimulates pDC secretion of high levels of type I interferons (IFN‐α/β). Study of SLE patients and murine disease models implicate these type I IFNs as key disease effectors. However, the role of pDC‐derived type I IFNs in regulating the inflammatory function of Th cells in SLE is unknown. Although, type I IFNs are classically considered to promote Th1‐mediated inflammation, they can also act as potent inhibitors of both Th1 and Th17 inflammatory cell responses. Work of ourselves and others leads us to hypothesize that if initiated during stages of SLE when Th cell‐mediated tissue inflammation is absent or minimal, such as early in the disease or during periods of remission, type I IFN neutralization will disrupt the cycle of systemic autoimmune induction and disease. However, if initiated during advanced stages of disease when there is substantial ongoing Th1 (and possibly Th17) cell‐mediated inflammation, targeting type I IFNs will exacerbate the Th cell‐mediated inflammatory disease and thus potentiate end‐organ damage and destruction. This has important implications for the application of the numerous anti‐type I IFN therapies currently under development for SLE treatment.