Polypeptide and immune modulation
The present invention relates to Roseburia flagellin, and/or a polynucleotide sequence encoding said Roseburia flagellin, and/or a vector comprising said polynucleotide sequence, and/or a host cell, including bacteria, comprising said vector, and/or a host cell, including bacteria, comprising said polynucleotide sequence, for use in modulating the inflammation of a tissue or an organ in a subject.
1. A method of reducing inflammation in a subject in need thereof, comprising administering to the subject a pharmaceutical composition that comprises an amount of a Roseburia flagellin polypeptide sufficient to increase a level of IL-10 in the subject, relative to a level of IL-10 prior to the administering, thereby reducing inflammation, wherein the Roseburia flagellin comprises a polypeptide sequence having at least 85% sequence identity to SEQ ID NO: 2, as determined by a sequence alignment performed using BLAST, and wherein the Roseburia flagellin comprises amino acids 79-117 of SEQ ID NO: 2 and binds to Toll-like receptor 5 (TLR5).
2. The method of claim 1 , wherein the Roseburia flagellin comprises a polypeptide sequence having at least 90% sequence identity to the polypeptide sequence of SEQ ID NO: 2, as determined by a sequence alignment performed using BLAST.
3. The method of claim 1 , wherein the Roseburia flagellin polypeptide comprises a polypeptide sequence having at least 95% sequence identity to the polypeptide sequence of SEQ ID NO: 2, as determined by a sequence alignment performed using BLAST.
4. The method of claim 1 , wherein the Roseburia flagellin polypeptide has at least 99% sequence identity to the polypeptide sequence of SEQ ID NO: 2, as determined by a sequence alignment performed using BLAST.
5. The method of claim 1 , wherein the Roseburia flagellin polypeptide has a polypeptide sequence of SEQ ID NO: 2.
6. The method of claim 1 , wherein the Roseburia flagellin polypeptide is a FlaA1 polypeptide.
7. The method of claim 1 , wherein the Roseburia flagellin polypeptide comprises a Roseburia hominis flagellin polypeptide or a Roseburia intestinalis flagellin polypeptide.
8. The method of claim 1 , wherein the pharmaceutical composition is an enteric formulation.
9. The method of claim 1 , wherein the administering is oral.
10. The method of claim 1 , wherein the administering is rectal.
11. The method of claim 1 , wherein the Roseburia flagellin polypeptide is comprised in a fusion protein.
12. The method of claim 1 , wherein the pharmaceutical composition is a solid composition.
13. The method of claim 1 , wherein the pharmaceutical composition is in the form of one or more tablets or capsules.
14. A method of modulating production of T cells in a subject, comprising administering to the subject a pharmaceutical composition comprising an amount of a Roseburia flagellin polypeptide sufficient to modulate the production of T cells in the subject, wherein the Roseburia flagellin comprises a polypeptide sequence having at least 85% sequence identity to SEQ ID NO: 2, as determined by a sequence alignment performed using BLAST, and wherein the Roseburia flagellin comprises amino acids 79-117 of SEQ ID NO: 2 and binds to Toll-like receptor 5 (TLR5).
15. The method of claim 14 , wherein the modulating comprises increasing the production of T cells.
16. The method of claim 14 , wherein the T cells comprise regulatory T cells.
17. The method of claim 14 , wherein the T cells are capable of expressing TLR5.