Signal tranducers and activators of transcription: Expression and function in anti-neutrophil cytoplasmic antibody-associated vasculitis

• Published in: Molecular medicine reports Vol. 9; no. 6; pp. 2316 - 2320
• Main Authors: WILDE, BENJAMIN, HOERNING, ANDRÉ, KRIBBEN, ANDREAS, WITZKE, OLIVER, DOLFF, SEBASTIAN
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.06.2014; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Aged; Analysis; anti-neutrophil cytoplasmic antibody; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - genetics; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - immunology; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - metabolism; Autoantibodies; Case-Control Studies; CD3 antigen; Cellular signal transduction; Cloning; Cytokines; Drug therapy; Female; Flow cytometry; Gene Expression Regulation; Genetic aspects; Genetic transcription; Homeostasis; Humans; Immunoglobulins; Immunoregulation; Interleukin 2; Interleukin-2 - metabolism; Interleukin-2 - pharmacology; Kinases; Lymphocytes; Lymphocytes T; Male; Middle Aged; Neutrophils; Patients; Peripheral blood; phosphorylated signal tranducer and activator of transcription 3; phosphorylated signal tranducer and activator of transcription 5; Phosphorylation; Risk factors; Signal Transduction; Stat3 protein; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Stat5 protein; STAT5 Transcription Factor - genetics; STAT5 Transcription Factor - metabolism; Studies; T cell receptors; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transcription factors; Transcription, Genetic; Vasculitis; Germany
• ISSN: 1791-2997; 1791-3004; 1791-3004
• DOI: 10.3892/mmr.2014.2062

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is an autoimmune small vessel vasculitis. Despite the role of autoantibodies, T cells play an essential role in pathogenesis and are abnormal in AAV. Signal transducers and activators of transcription (STAT) affect immunoregulation and T-cell homeostasis. Therefore, the present study examined the ex vivo basal expression of the activated forms of STAT5 [phosphorylated (p)STAT5] and STAT3 (pSTAT3) in AAV and analyzed the function of two signaling pathways linked to these transcription factors. In total, 31 patients with AAV and 16 age-matched healthy controls (HCs) were enrolled. CD3+ T cells from peripheral blood were analyzed directly ex vivo by a fluorescence-activated cell sorter for basal expression of pSTAT5 and pSTAT3. Expression was also analyzed in T cells following short-term stimulation with interleukin (IL)-2 or -10. The basal expression of pSTAT5/3 in T cells was similar to AAV patients and HC. Following stimulation with IL-2 or -10, expression of pSTAT5/3 increased in AAV subjects compared with HC. Basal expression of pSTAT3 correlated with the relapse rate in AAV. In conclusion, STAT3 and STAT5 mediated signaling pathways were functionally intact in AAV patients and exhibited hyper-responsiveness to IL-2 and -10 stimuli. Thus, T-cell abnormalities in AAV are not promoted by an altered basal expression of pSTAT5/3 or dysfunction of the IL-2/-10 signaling pathways, in which STAT5/3 are essential.