PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with reciprocal balance of Th17 and Tregs

• Published in: Scientific reports 2016-10, Vol.6 (1), p.34617-34617, Article 34617
• Main Authors: Lee, Seung Hoon, Park, Jin-Sil, Byun, Jae-Kyung, Jhun, JooYeon, Jung, KyungAh, Seo, Hyeon-Beom, Moon, Young-Mee, Kim, Ho-Youn, Park, Sung-Hwan, Cho, Mi-La
• Format: Article
• Language: English
• Subjects: 42/44; 631/250/251; 631/250/38; Animals; Arthritis; Arthritis, Experimental - genetics; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Cell Differentiation; Gene Expression Regulation; Humanities and Social Sciences; Inactivation; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Knockout; multidisciplinary; Plasmids - administration & dosage; Plasmids - chemistry; Plasmids - metabolism; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - immunology; Rheumatoid arthritis; Science; Severity of Illness Index; Signal Transduction; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - immunology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology; Th17 Cells - immunology; Th17 Cells - pathology; Tumor Suppressor Protein p53 - deficiency; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - immunology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep34617

PTEN is a tyrosine phosphatase with significant function in inhibiting STAT3 activation. Recently, inactivation of STAT3 has been demonstrated as a therapeutic candidate for autoimmune arthritis. The expression of PTEN controlled by p53 regulates autoimmune arthritis through modulating the balance between Th17 and Treg. We hypothesized that PTEN regulated by p53 might reduce CIA severity and inflammatory response via inhibiting STAT3 activation. Our results revealed that PTEN could ameliorate experimental autoimmune arthritis by reducing STAT3 activity and Th17 differentiation. Systemic infusion of PTEN overexpression downregulated CIA severity. In addition, PTEN overexpression decreased the activation of T cells and modulated reciprocal differentiation of Th17 and Treg cells. We observed that PTEN expression downregulated by p53 deficiency induced the activation of STAT3. Loss of p53 exacerbated autoimmune arthritis and dysregulated the population of Th17 and Treg. These data suggest that induction of STAT3-modulatory activity of PTEN may be a therapeutic target for rheumatoid arthritis therapy.