IL-12 p35 silenced dendritic cells modulate immune responses by blocking IL-12 signaling through JAK-STAT pathway in T lymphocytes.
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.
Xu
Hao
H
Department of General Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210009, China.
Zhang
Yuhua
Y
Hua
Yibing
Y
Chen
Tao
T
Wang
Haiquan
H
Wu
Wenxi
W
D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D018664:Interleukin-12 / Q000378:metabolism / Q000502:physiology*; D053765:Interleukin-12 Subunit p35 / Q000494:pharmacology*; D053614:Janus Kinase 2 / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D011920:Rats, Inbred WF; D050791:STAT Transcription Factors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000502:physiology*
D053765:Interleukin-12 Subunit p35; D034741:RNA, Small Interfering; D050791:STAT Transcription Factors; D018664:Interleukin-12; C507927:Jak2 protein, rat; D053614:Janus Kinase 2