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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/23099

Title: Production of proinflammatory cytokines by monocytes in liver transplanted recipients with de novo automimmune hepatitis is enhanced and induces TH1-like regulatory T cells
Other Titles: Pro-inflammatory TH1-like and TH17-like FOXP3+ 4 Tregs in DAIH
Authors: Arterbery, Adam S.
Asofo-Addo, Awo
Avitzur, Yaron
Ciarleglio, Maria
Deng, Yanhong
Lobritto, Steven J.
Martinez, Mercedes
Hafler, David A.
Kleinewietfeld, Markus
Ekong, Udeme D.
Issue Date: 2016
Citation: JOURNAL OF IMMUNOLOGY, 196(10), p. 4040-4051
Abstract: A subset of human regulatory T cells (Tregs) can secrete IFN-γ or IL-17 and thus share features of TH1 or TH17 effector cells, and lose suppressive function. The main factors driving this differentiation of Tregs towards a pro-inflammatory phenotype include IL-12 for TH1-like and IL-6 for TH17-type Tregs. In this study we show that Tregs of patients with de novo autoimmune hepatitis (dAIH) display increased frequencies of pro-inflammatory IFN-γ and IL-17 cytokines. Irrespective of a fully demethylated FOXP3 locus, Tregs of subjects with de novo autoimmune hepatitis are functionally impaired. In line with the observed Treg phenotype, we detected the presence of two dominant cytokines (IL-12 and IL-6) clustering with CD68+ monocyte/macrophage cells in livers of subjects with de novo autoimmune hepatitis and isolated monocytes of subjects with de novo autoimmune hepatitis secrete high levels of pro-inflammatory IL-12 and IL-6 suggesting that this inflammatory milieu is key for functional impairment of Tregs. Importantly, the blockade of IFN-γ partially restores suppressive function of Tregs of subjects with de novo autoimmune hepatitis indicating that monocyte/macrophage derived triggers might play a central role in Treg dysfunction and pathogenesis of de novo autoimmune hepatitis.
URI: http://hdl.handle.net/1942/23099
DOI: 10.4049/jimmunol.1502276
ISI #: 000375831200007
ISSN: 0022-1767
Category: A1
Type: Journal Contribution
Validation: ecoom, 2017
Appears in Collections: Research publications

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