PMID- 24676862 OWN - NLM STAT- MEDLINE DCOM- 20150105 LR - 20140423 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 9 IP - 6 DP - 2014 Jun TI - Signal tranducers and activators of transcription: expression and function in anti-neutrophil cytoplasmic antibody-associated vasculitis. PG - 2316-20 LID - 10.3892/mmr.2014.2062 [doi] AB - 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. FAU - Wilde, Benjamin AU - Wilde B AD - Department of Nephrology, University Hospital Essen, University of Duisburg‑Essen, Essen, North Rhine‑Westphalia 45122, Germany. FAU - Hoerning, Andre AU - Hoerning A AD - Department of Pediatrics II, Pediatric Nephrology, Gastroenterology, Endocrinology and Transplant Medicine, Children's Hospital Essen, University of Duisburg‑Essen, Essen, North Rhine‑Westphalia 45122, Germany. FAU - Kribben, Andreas AU - Kribben A AD - Department of Nephrology, University Hospital Essen, University of Duisburg‑Essen, Essen, North Rhine‑Westphalia 45122, Germany. FAU - Witzke, Oliver AU - Witzke O AD - Department of Nephrology, University Hospital Essen, University of Duisburg‑Essen, Essen, North Rhine‑Westphalia 45122, Germany. FAU - Dolff, Sebastian AU - Dolff S AD - Department of Nephrology, University Hospital Essen, University of Duisburg‑Essen, Essen, North Rhine‑Westphalia 45122, Germany. LA - eng PT - Journal Article DEP - 20140320 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Interleukin-2) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT5 Transcription Factor) SB - IM MH - Aged MH - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/*genetics/immunology/*metabolism MH - Case-Control Studies MH - Female MH - *Gene Expression Regulation MH - Humans MH - Interleukin-2/metabolism/pharmacology MH - Male MH - Middle Aged MH - Phosphorylation MH - STAT3 Transcription Factor/genetics/metabolism MH - STAT5 Transcription Factor/genetics/metabolism MH - *Signal Transduction MH - T-Lymphocytes/drug effects/immunology/metabolism MH - *Transcription, Genetic EDAT- 2014/03/29 06:00 MHDA- 2015/01/06 06:00 CRDT- 2014/03/29 06:00 PHST- 2013/09/21 00:00 [received] PHST- 2014/02/07 00:00 [accepted] PHST- 2014/03/29 06:00 [entrez] PHST- 2014/03/29 06:00 [pubmed] PHST- 2015/01/06 06:00 [medline] AID - 10.3892/mmr.2014.2062 [doi] PST - ppublish SO - Mol Med Rep. 2014 Jun;9(6):2316-20. doi: 10.3892/mmr.2014.2062. Epub 2014 Mar 20.