A mutated IL-34 polypeptide comprising, or consisting of, an amino acid sequence selected from the group consisting of: a) the 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 the serine residue at position 100 of SEQ ID NO: 1 is substituted by a phenylalanine residue (S100F), b) an amino acid sequence having at least 90% of sequence identity with the amino acid sequence defined in a), wherein the serine residue at the position corresponding to position 100 of SEQ ID NO: 1 is substituted by a phenylalanine residue (S100F), provided that said polypeptide has a superior agonist activity compared to wild-type IL-34 having the 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, and c) a fragment of a sequence defined in a) or b), wherein said fragment comprises from 200 to 222 contiguous amino acid residues of the sequence defined in a) or b) and wherein the serine residue at the position corresponding to position 100 of SEQ ID NO: 1 is substituted by a phenylalanine residue (S100F), provided that said polypeptide has a superior agonist activity compared to wild-type IL-34 having the 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 the agonist activity is at least one, preferably at least two, of: - a binding affinity towards CSF-1R, PTP-ζ and/or CD138, - a capacity at inducing or enhancing the survival and proliferation of monocytes, preferably of CD14 + monocytes, - a capacity at inducing or enhancing the differentiation of monocytes, preferably of CD14 + monocytes, into macrophages, and - a capacity at inducing or enhancing the phosphorylation of kinases, preferably of protein kinase B (Akt) and/or extracellular signal-regulated kinases 1/2 (ERK1/2). a) the 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 the serine residue at position 100 of SEQ ID NO: 1 is substituted by a phenylalanine residue (S100F), b) an amino acid sequence having at least 90% of sequence identity with the amino acid sequence defined in a), wherein the serine residue at the position corresponding to position 100 of SEQ ID NO: 1 is substituted by a phenylalanine residue (S100F), provided that said polypeptide has a superior agonist activity compared to wild-type IL-34 having the 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, and c) a fragment of a sequence defined in a) or b), wherein said fragment comprises from 200 to 222 contiguous amino acid residues of the sequence defined in a) or b) and wherein the serine residue at the position corresponding to position 100 of SEQ ID NO: 1 is substituted by a phenylalanine residue (S100F), provided that said polypeptide has a superior agonist activity compared to wild-type IL-34 having the 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; - a binding affinity towards CSF-1R, PTP-ζ and/or CD138, - a capacity at inducing or enhancing the survival and proliferation of monocytes, preferably of CD14 + monocytes, - a capacity at inducing or enhancing the differentiation of monocytes, preferably of CD14 + monocytes, into macrophages, and - a capacity at inducing or enhancing the phosphorylation of kinases, preferably of protein kinase B (Akt) and/or extracellular signal-regulated kinases 1/2 (ERK1/2).