IFN-γ and IL-17: the two faces of T-cell pathology in giant cell arteritis
Year: 2010
Type: article
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.
Source: Current Opinion in Rheumatology
Institutions: Stanford Medicine, Stanford University, Mayo Clinic
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: CD8 T Cells in Rheumatoid Arthritis, G2042391711, G2540523102, Oligoclonal T Cell Expansion and Rheumatoid Arthritis, G429955531, G64106078, Ocular Disease in Giant Cell Arteritis, Interactions Between Inflammation, Oxidant Stress and Cardiovascular Disease, G7126395394, Vaccine and Infection Induced Immunity in the Young and Aged, G971417677
OpenAlex ID: W2084885786