Mutated interleukin-34 (IL-34) polypeptides and uses thereof in therapy
AssigneesINSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) Paris, FRANCE, Universite De Nantes
InventorsCarole Guillonneau, Ignacio Anegon, Erwan Mortier, Agnès Quemener
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Abstract
Interleukin-34 is a cytokine that is involved in the differentiation and survival of macrophages, monocytes, and dendritic cells in response to inflammation. The involvement of IL-34 has been shown in areas as diverse as neuronal protection, autoimmune diseases, infection, cancer, and transplantation. Recent work has also demonstrated a new and possible therapeutic role for IL-34 as a Foxp3+ Treg-secreted cytokine mediator of transplant tolerance. New mutated IL-34 polypeptides have been generated, which can be used as agonists or antagonists.
Claims12
A mutated interleukin-34 (IL-34) polypeptide comprising
- an amino acid sequence ranging from the asparagine residue at position 21 of SEQ ID NO:
- 1 to the proline residue at position 242 of SEQ ID NO:
- 1, wherein one or more mutations have been introduced, said one or more mutations being selected from the group consisting of:
- a substitution of the serine residue at position 100 by a phenylalanine residue (S100F),
- a substitution of the threonine residue at position 36 by a tyrosine residue (T36Y),
- a substitution of the glutamine residue at position 131 by a phenylalanine residue (Q131F),
- a substitution of the threonine residue at position 36 by a tryptophan residue (T36W),
- a substitution of the threonine residue at position 36 by a phenylalanine residue (T36F),
- a substitution of the histidine residue at position 56 and of the glycine residue at position 112 by a cysteine residue (H56C and G112C), and
- combinations thereof.
A mutated IL-34 polypeptide comprising
- an amino acid sequence ranging from the asparagine residue at position 21 of SEQ ID NO:
- 1 to the proline residue at position 242 of SEQ ID NO:
- 1, wherein one or more mutations have been introduced, said one or more mutations being selected from the group consisting of:
- a substitution of the serine residue at position 100 by an aspartic acid residue (S100D),
- a substitution of the glutamine residue at position 131 by an arginine residue (Q131R), and
- a combination thereof.
Dependencies are inferred from the claim text.