Recently, Prof. Gao Chengjiang’s research team in the Institute of Immunology at Shandong University Medical School made series of important progresses in the field of innate immune regulation.

They discovered that TLR activation induces the expression of ubiquitin E3 ligase Tripartite Motif-Containing Protein 38 (TRIM38) and TRIM38 negatively regulates TLR-induced immune responses by promoting K48-linked polyubiquitination and proteasomal degradation of TNF receptor associated factor 6 (TRAF6). This finding was published as a highlighted article in the Journal of Immunology (2012, 188(6):2567-2574).

Furthermore, they demonstrated that TRIM38 could negatively regulate TLR3/4- and RIG-I-mediated IFN-β production and antiviral response by targeting NF-κB-activating kinase-associated protein 1 (NAP1) for ubiquitination and subsequent proteasome-mediated degradation (Journal of Immunology, 2012 Apr 25. Epub ahead of print). They found ubiquitin E3 ligase Smurf1 negatively regulates IFN-γ signaling and antiviral response by promoting STAT1 polyubiquitination and degradation (Journal of Biological Chemistry, 2012 Apr 2. Epub ahead of print). They also noted that heterogeneous nuclear ribonucleoprotein U (hnRNP U) induced by TLR signaling binds to the mRNA of a subset of pro-inflammatory cytokines (TNF-α、IL6 and IL-1β) and positively regulates the expression of these cytokines by stabilizing mRNA (Journal of Immunology, 2012, 188(7):3179-3187).

Innate immunity is the first line of the defensive mechanisms that protect hosts from invading microbial pathogens. Host cells express various pattern recognition receptors (PRRs) including Toll-like receptor (TLR) and Retinoic acid-inducible gene I (RIG-I), which are evolutionarily conserved to recognize PAMPs. Recognition of PAMPs by PRRs will lead to the activation of intracellular signaling pathways that culminate in the induction of proinflammatory cytokines, chemokines, interferons (IFNs), and consequently initiate innate immunity and enhance adaptive immunity. While full activation of innate immune responses is necessary for eliminating invading pathogens, uncontrolled immune responses activation might be involved in the pathogenesis of autoimmune, chronic inflammatory and infectious diseases.

These findings will obviously facilitate the development of new strategies to control these diseases and supply a new viewpoint on innate immune signal transduction and provide new target for the drug design and vaccine development.

These works were mainly carried out by lecturer Zhao Wei, graduate student Wang Lijuan, Yuan Chao, Zhang Meng in the Department of Immunology and supported by grants from National Natural Science Foundation of China, Taishan Scholar Program of Shandong Province and Shandong Provincial Nature Science Foundation for Distinguished Young Scholars.

Written by: Gao Peng

Edited by: Lawrence Phillips, Jing Zizhao

Source: School of Medicine,www.view.sdu.edu.cn