SCIENCE

Toll Like Receptors (TLRs) are pattern recognition receptors present on various immune cells designed to recognize molecular motifs shared by various microorganisms (MAMPs). Binding of molecular motifs to TLRs enable the immune system to immediately react against invading micro-organisms. 

Although TLRs are primarily activated by MAMPs, they can also be activated by certain endogenous “danger” molecules, also called damage-associated molecular patterns (DAMPs). DAMPs can be classified in 4 groups; (1) Those produced by degradation of the extra-cellular matrix, such as hyaluronan fragments; (2) Those upregulated during inflammation, such as S100 proteins, serum amyloid A3 and tenascin. (3) Those released from necrotic cells such as high-mobility group proteins (HMGB-1) and endogenous nucleic acids and (4) Self proteins that become chemically modified by oxidation and or citrullination such as citrullinated fibrinogen (1)

 

Rheumatoid Arthritis is one of the most prevalent autoimmune diseases that is characterized by a chronic inflammatory reaction that leads to tissue destruction in joints. Although the origin of the disease may be undefined, genetic predisposition and environmental risk factors are believed to be involved in the development of the disease. Increased TLR expression on synovial lining and infiltrating immune cells are observed in patients with RA and are believed to play a key role in a self-sustaining chronic inflammatory loop by continuous activation with DAMPs creating a positive feedback loop further amplifying the inflammatory reaction in the joints.

TLR10 is so far without a know function. We have shown that TLR10 acts as an inhibitory receptor with suppressive effects on pro-inflammatory cytokine production induced by other TLRs such as TLR2 (2).  Furthermore, TLR10 activation results in an increase of the production of endogenous anti-inflammatory IL1Ra further dampening inflammatory processes.

1.    Nature Reviews (2016) vol 12: 344-357

2.  PNAS USA (2014) Oct 21 111(42): E4478-E4484

REFERENCES

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