IFN-γ and IL-17: The two faces of T-cell pathology in giant cell arteritis

Cornelia M. Weyand, Brian R. Younge, Jörg J. Goronzy

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

Purpose of review: Granuloma formation in giant cell arteritis (GCA) emphasizes the role of adaptive immunity and highlights the role of antigen-specific T cells. Recent data demonstrate that at least two separate lineages of CD4 T cells participate in vascular inflammation, providing an important clue that multiple disease instigators may initiate pathogenic immunity. Recent finding: IFN-γ-producing Th1 cells and IL-17-producing Th17 cells have been implicated in GCA. Patients with biopsy-positive GCA underwent two consecutive temporal artery biopsies, one prior to therapy and one while on corticosteroids. In untreated patients, Th1 and Th17 cells co-existed in the vascular lesions. Following therapy, Th17 cells were essentially lost, whereas Th1 cells persisted almost unaffected. In the peripheral blood of untreated patients Th17 frequencies were increased eight-fold, but normalized with therapy. Blood Th1 cells were doubled in frequency, independent of therapy. Corticosteroids functioned by selectively suppressing IL-1β, IL-6 and IL-23-releasing antigen-presenting cells (APCs), disrupting induction of Th17 cells. Summary: At least two distinct CD4 T-cell subsets promote vascular inflammation in GCA. In early disease, APCs promote differentiation of Th17 as well as Th1 cells. Chronic disease is characterized by persistent Th1-inducing signals, independent of IL-17-mediated inflammation. More than one disease instigator may trigger APCs to induce multiple T-cell lineages. Cocktails of therapies will be needed for appropriate disease control.

Original languageEnglish (US)
Pages (from-to)43-49
Number of pages7
JournalCurrent opinion in rheumatology
Volume23
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • antigen-presenting cell
  • IFN-γ
  • IL-17
  • T cell

ASJC Scopus subject areas

  • Rheumatology

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