Seminar: Prof. Glen N. Barber, Ph.D.: STING, Innate Immune Signaling and Self DNA-Activated Inflammatory Disease

Immune Signal Unit (Ishikawa Unit) would like to invite you to the Seminar by Professor Glen N. Barber, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine.

Date:     Tuesday, December 3^rd, 2013

Time:    15:00 – 16:00

Venue:  C016, Lab 1, Level C

Speaker:             Glen N. Barber, Ph. D., Professor and Chair Cell Biology Department

 Associate Director for Basic Research,Sylvester Comprehensive Cancer Center, University of Miami School of Medicine

Title:     STING, Innate Immune Signaling and Self DNA-Activated Inflammatory Disease.

Abstract:

We have recently reported that STING (stimulator of interferon genes) is essential for controlling Toll-Like Receptor (TLR)-independent, cytosolic DNA-mediated innate immune signaling. Accordingly, STING appears essential for protecting the host against lethal disease following infection by pathogens such as HSV1. Such cellular DNA sensors may also play a key role in triggering inflammation aggravated autoimmune diseases. Autoimmune diseases such as systemic lupus erythematosus (SLE) affect millions worldwide. For example, SLE and diseases such as Aicardi-Goutieres syndrome (AGS) are characterized by the overproduction of cytokines such as type I interferon (IFN) suggesting that stimulation of host innate immune responses, speculatively by chronic infection or self nucleic acids, play a role in the manifestation of these diseases. It is known that mice lacking DNAse II die during embryonic development through comparable autoimmune disease since phagocytosed DNA from apoptotic cells cannot be adequately digested and intracellular host DNA sensors are activated resulting in the production of a variety of cytokines including type I IFN. However, we have found that STING complexes with phagocytosed undigested DNA and controls innate immune signaling events that facilitate such events.  DNase II-dependent autoimmune embryonic lethality was rescued by loss of STING function and polyarthritis completely prevented since cytosolic DNA failed to robustly trigger cytokine production through STING controlled signaling pathways. Consequently, loss of STING expression similarly alleviated Trex1-dependent lethal inflammatory myocarditis in mice, a model for AGS, speculatively caused by endogenous self DNA. Our data provides molecular insight into the causes of DNA-mediated inflammation-dependent autoimmune disorders and affords a new target that could plausibly be therapeutically controlled, to help prevent such diseases.

References:

• Ishikawa H. and Barber GN (2008) Nature 455, 674-678
• Ishikawa H. et al (2009) Nature 461, 788-792
• Chen H. et al (2011) Cell 147, 436-446
• Ahn J. et al (2012) PNAS 109, 19386-19391
• Konno H. et al (2013) Cell 24, 688-698
• Abe T. et al (2013) Mol. Cell 50, 5-15

We hope to see many of you at the Seminar.

Best Regards,
Rika Yoshizawa
Immune Signal Unit (Ishikawa Unit)