Deficiency of STING Promotes Collagen-Specific Antibody Production and B Cell Survival in Collagen-Induced Arthritis

Abstract

The levels of interferon-alpha are high in the serum and synovial fluid of rheumatoid arthritis (RA) patients. Activation of the stimulator of type I interferon genes (STING) mediates the productions of type I interferon and promotes chronic inflammation. STING plays a significant role in autoimmune lupus mice. However, the function of STING in collagen-induced arthritis (CIA) model has never been described. This study aimed to test the function of STING in CIA. The Sting-deficient mice developed arthritis comparable to WT mice. The levels of anti-collagen antibody from Sting-deficient mice were significantly higher than the WT mice. The B cells derived from Sting-deficient mice showed better survival than WT mice in response to the B cell receptor (BCR) stimulation. Activation of STING also induced B cell death, especially in activated B cells. This study demonstrated that the inhibition of STING promotes anti-collagen antibodies and B cell survival, which suggested that STING acts as a negative regulator of B cell function in the CIA model.

The STING1 network regulates autophagy and cell death

“…Therefore, the combined use of STING1 agonists (e.g., using ADU-S100) and immune checkpoint inhibitors may be the best strategy for tumor treatment 182 , 183 . In addition, STING1 activation can impair immunotherapy because it is a mediator of IFN-induced cell death of B cells 184 or T cells 185 . Consequently, STING1 inhibitors (Table 1 ) can alleviate the side effects of STING1 overactivation.…”

Novel STING-targeted PET radiotracer for alert and therapeutic evaluation of acute lung injury

“…Secondly, given the key role of STING in the initiation of innate immunity, [ 18 F]FBTA may also provide warning signals for other diseases besides ALI, such as rheumatoid arthritis 41 and myocardial infarction 42 , etc.. Thirdly, in order to identify drugs for the treatment of ALI, the [ 18 F]FBTA-PET can also be used as a rapid and visual assessment tool for screening effective drugs in the future.…”

Inhibitory targeting cGAS-STING-TBK1 axis: Emerging strategies for autoimmune diseases therapy

“…Deoxyribonuclease II (DNase II) can degrade DNA by hydrolyzing its phosphodiester bonds to prevent its abnormal accumulation. The lack of DNase II prevents this process and promotes STING activation and IFN-dependent systemic auto-inflammation, such as collagen-induced arthritis (CIA) ( Figure 7B ) ( 128 , 129 ). STING gene-deficient mice had significantly higher levels of anti-collagen antibodies and showed better survival rates than wild-type (WT) mice ( 128 ).…”

“…The lack of DNase II prevents this process and promotes STING activation and IFN-dependent systemic auto-inflammation, such as collagen-induced arthritis (CIA) ( Figure 7B ) ( 128 , 129 ). STING gene-deficient mice had significantly higher levels of anti-collagen antibodies and showed better survival rates than wild-type (WT) mice ( 128 ). STING promotes the expression of IFN-inducible genes and the expansion of dendritic cells in CIA.…”