Abstract: Provided herein are compositions that immunospecifically bind to Siglec-15, small molecules, peptides, or other entities that may bind Siglec-15 in a similar fashion. Methods of use are provided for Siglec-15 targeting therapeutics to restore bone homeostasis by inhibiting bone resorption and increase bone formation, specifically in non-ambulatory people or in people with disuse osteoporosis. The therapeutics referenced here may be used to overcome the need for mechanical loading on the bone to maintain high quality skeleton.

Abstract: Compositions and methods of use thereof for modulating LAIR-1 are provided. For example, immunomodulatory agents are provided that reduce LAIR-1 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to increase an immune response in a subject in need thereof. Exemplary agents include (i) a soluble LAIR-2 polypeptide or fusion protein, (ii) a soluble LAIR-1 polypeptide or fusion protein, (iii) a function blocking anti-LAIR-1 antibody, (iv) an antibody that depletes LAIR-1 positive cells, and (y) combinations thereof. Immunomodulatory agents are also provided that increase LAIR-1 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to reduce an immune response in a subject in need thereof. Exemplary agents include: (i) a function activating anti-LAIR-1 antibody, (ii) a function blocking anti-LAIR-2 antibody, and (iii) a combination thereof.

Abstract: Compositions and methods of use thereof for modulating FLRT3 mediated signaling are provided. For example, immunomodulatory agents are provided that reduce FLRT3 expression, ligand binding, crosslinking, FLRT3 mediated signaling, or a combination thereof. In another embodiment, immunomodulatory agents are provided that enhance or promote FLRT3 expression, ligand binding, crosslinking, FLRT3 mediated signaling, or a combination thereof. Such agents can be used to modulate an immune response in a subject in need thereof.

Abstract: Siglec-15 binding molecules are provides. The molecules are typically an antibody or antigen binding fragment thereof that immunospecifically binds to Siglec-15. Siglec-15 ligand-binding molecules are also provided. The molecules are typically Siglec-15 polypeptide or fusion protein. Methods of using the molecules to reduce Siglec-15 mediated immunosuppression in a subject in need thereof are also provided.