Modified Cpn10 and PRR signalling
The present invention relates to isolated Cpn10 polypeptides possessing an increased affinity for a PRR ligand compared to Ala Cpn10 polypeptide. In a further embodiment, the present invention also relates to modified chaperonin 10 polypeptides, and to nucleic acids encoding the same and to compositions comprising such polypeptides and uses thereof.
1. An isolated Cpn10 polypeptide possessing an increased affinity for a PRR ligand compared to Ala-Cpn10 polypeptide, the isolated Cpn10 polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO:58, SEQ ID NO:88, SEQ ID NO:91, SEQ ID NO:94, SEQ ID NO:181, SEQ ID NO:193, SEQ ID NO:229, SEQ ID NO:256, SEQ ID NO:259, SEQ ID NO:304, SEQ ID NO:310, SEQ ID NO:328 and SEQ ID NO:349.
2. The polypeptide of claim 1 , wherein said PRR ligand modulates the signaling of PRRs selected from the group consisting of a Toll-like Receptor (TLR), Nucleotide-binding domain LRR-containing family (NLR), a RIG-I-like receptor (RLR), a DNA-dependent activator of IRF (DAI), a C-type Lectin receptor (CLR) or a member of the IFl20X/IFl16 family (e.g. 1fi16, Aim2, MNDA and IFIX).
3. The polypeptide of claim 1 , wherein said TLR is selected from the group consisting of at least one of TLR3, TLR7, TLR8 or TLR9.
4. A method for treating a disease, disorder or condition in a subject in need of treatment thereof, the method comprising administering to the subject an effective amount of a polypeptide according to claim 1 .
5. The method of claim 4 , wherein said disease, disorder or condition is selected from: rheumatoid arthritis, GVHD, and psoriasis.
6. A pharmaceutical composition comprising a polypeptide according to claim 1 .
7. A method for modulating PRR signaling in a subject in need thereof, or in at least one cell tissue or organ thereof, the method comprising administering a therapeutically effective amount of a polypeptide according to claim 1 .