Toll-like receptors (TLR) 7 and 8 fact sheet
About TLR 7/8
A healthy immune response to pathogens plays a key role in protection from infection.
Toll-like receptors (TLR) 7 and 8 help detect the presence of certain pathogens in the body and help initiate and amplify both innate (nonspecific) and adaptive (specialized or specific) immune responses.1,2
These receptors in immune cells normally recognize single-stranded RNA (ssRNA) from pathogens (such as certain viruses) and activate various immune cells, resulting in an immune response.1,2
TLR 7/8 and Inflammatory Diseases
An uncontrolled or
misdirected immune
response by the body
can contribute to the
damage of otherwise
healthy cells, resulting in
immune-mediated
diseases.
Overactivation of
TLR7/8 contributesto
inflammation that occurs
in immune-mediated
diseases.1,3
TLR7/8 can become
overstimulated when
the receptors recognize
and are activated by
ssRNA released by
damaged tissue.1,3
Certain immune-mediated diseases, such as systemic lupus erythematosus, are associated with defects in the body’s ability to eliminate cell debris from tissue damage, which can activate TLR7/8 and further contribute to the disease.4
TLR7 gain-of-function genetic variations may also be a driver for systemic lupus erythematosus.5
Research Implications
Researchers are investigating potential ways to prevent the activation of the TLR7/8 pathway by blocking the receptors with small molecule inhibitors.6,7
This inhibition may help in the treatment of a range of immune-mediated diseases, such as lupus and other rheumatic diseases.7
At Bristol Myers Squibb, our investigation of immune pathways and receptors like TLR7/8 helps to deepen our understanding of disease and causal human biology and further our efforts to deliver meaningful solutions to patients with immune-mediated diseases.
REFERENCES:
- Hayashi T, Gray CS, Chan M, et al. Prevention of Autoimmune Disease by Induction of Tolerance to Toll-like Receptor 7. Proc Natl Acad Sci U S A. 2009;106(8):2764-2769. doi: 10.1073/pnas.0813037106.
- Arpaia N, Barton GM. Toll-like Receptors: Key Players in Antiviral Immunity. Curr Opin Virol. 2011;1(6):447-454. doi:10.1016/j.coviro.2011.10.006
- Fillatreau S, Manfroi B, Dörner T. Toll-like receptor signalling in B cells during systemic lupus erythematosus. Nat Rev Rheumatol. 2021;17(2):98-108. doi:10.1038/s41584-020-00544-4.
- Shao WH, Cohen PL. Disturbances of apoptotic cell clearance in systemic lupus erythematosus. Arthritis Res Ther. 2011;13(1):202. doi:10.1186/ar3206.
- Brown GT, Cañete PF, Wang H, et al. TLR7 gain-of-function genetic variation causes human lupus. Nature. 2022;(605):349-356. doi: 10.1038/s41586-022-04642-z.
- Mussari CP, Dodd DS, Sreekantha RK, et al. Discovery of Potent and Orally Bioavailable Small Molecule Antagonists of Toll-like Receptors 7/8/9 (TLR7/8/9). ACS Med Chem Lett. 2020;11(9):1751-1758. doi:10.1021/acsmedchemlett.0c00264.
- Sreekantha RK, Mussari CP, Dodd DS, et al. Identification of 2-Pyridinylindole-Based Dual Antagonists of Toll-like Receptors 7 and
- (TLR7/8). ACS Med Chem Lett. 2022;13(5): 812–818. doi:10.1021/acsmedchemlett.2c00049.