IL-12 p35 silenced dendritic cells modulate immune responses by blocking IL-12 signaling through JAK-STAT pathway in T lymphocytes

• Published in: Biochemical and biophysical research communications 2007-02, Vol.353 (3), p.812-816
• Main Authors: Xu, Hao, Zhang, Yuhua, Hua, Yibing, Chen, Tao, Wang, Haiquan, Wu, Wenxi
• Format: Article
• Language: English
• Subjects: Animals; Cytokine signaling; Dendritic cell; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - physiology; Immunomodulation; Interleukin-12; Interleukin-12 - metabolism; Interleukin-12 - physiology; Interleukin-12 Subunit p35 - pharmacology; Janus Kinase 2 - physiology; Rats; Rats, Inbred WF; RNA interference; RNA, Small Interfering - pharmacology; Signal Transduction - drug effects; STAT Transcription Factors - physiology; T-Lymphocytes - physiology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.12.108

Dendritic cells (DC) constitute a complex system of uniquely specialized antigen-presenting cells (APC) that play crucial roles in the initiation and regulation of immune responses. Recent studies have demonstrated that DC silenced by siRNA IL-12 p35 showed tolerogenic capacity in vitro. However, their mechanism of action is not fully understood. In this study, IL-12p35 siRNA was chemically synthesized and transfected into DCs. A coculture of T cells and DCs was performed. After 30 min coculture, T cells were harvested and analyzed. We showed that the IL-12 p35 silenced DCs decreased IL-12-induced T cell responses through blocking tyrosine phosphorylation of JAK2, TYK2, STAT3, and STAT4 proteins in T cells. These results demonstrate IL-12 p35 silenced DCs modulate immune responses by blocking IL-12 signaling through JAK-STAT pathway in T cells.