Abstract: The present invention is directed towards isolated antibodies that bind to IL12R?1. Specifically, anti-IL12R?1 antibodies, and methods of treatment using the antibodies are disclosed. The antibody is targeted against the beta 1 subunit of the receptors of IL-12 and IL-23 and is capable of blocking signaling by inflammatory cytokines IL-12 and IL-23, which could be useful in treating autoimmune inflammatory diseases, such as inflammatory bowel disease (IBD), RA, and psoriasis.

Abstract: The present disclosure is directed to a method for treating a microglial dysfunction-associated neurodegenerative disease in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of a composition comprising a microglia receptor agonist that directly activates SYK.

Abstract: Among the various aspects of the present disclosure is the provision of methods and compositions for reducing checkpoint immunotherapy resistance or enhance checkpoint immunotherapy efficacy comprising treatment with a TREM2 inhibiting agent having reduced Fc effector function.

Abstract: Among the various aspects of the present disclosure is the provision of methods and compositions for modulating the Natural Cyotoxicity Receptor 2 (NCR2).

Abstract: The present disclosure is directed to a method for treating a microglial dysfunction-associated neurodegenerative disease in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of a composition comprising a microglia receptor agonist that directly activates SYK.

Abstract: The present invention is directed towards isolated antibodies that bind to IL12R?1. Specifically, anti-IL12R?1 antibodies, and methods of treatment using the antibodies are disclosed. The antibody is targeted against the beta 1 subunit of the receptors of IL-12 and IL-23 and is capable of blocking signaling by inflammatory cytokines IL-12 and IL-23, which could be useful in treating autoimmune inflammatory diseases, such as inflammatory bowel disease (IBD), RA, and psoriasis.

Abstract: Among the various aspects of the present disclosure is the provision of methods of treating a microglial dysfunction-associated diseases, disorder, and conditions. The present disclosure provides for a method for treating microglial dysfunction in a subject having a microglial dysfunction-associated neurodegenerative disease comprising administering to a subject a therapeutically effective amount of a microglial rescuing agent. The present disclosure also provides for a method of reversing neuronal damage in a subject having a microglial dysfunction-associated neurodegenerative disease, wherein the microglial dysfunction-associated neurodegenerative disease is characterized by a single nucleotide polymorphisms (SNPs) or mutation in Trem2 or ApoE affecting microglial functions.

Abstract: The present invention provides TREM2 constructs. TREM2 constructs of the invention are polynucleotide sequences encoding a polypeptide, wherein the polypeptide comprises at least one TREM2 or fragment thereof and a targeting moiety and optionally comprising a signal peptide and/or a purification moiety. The present invention also provides isolated polypeptides encoded by TREM2 constructs, vectors comprising TREM2 constructs, isolated cells comprising said vectors, and methods of use thereof.

Abstract: Among the various aspects of the present disclosure is the provision of methods and compositions for modulating the Natural Cyotoxicity Receptor 2 (NCR2).

Abstract: The present invention provides TREM2 constructs. TREM2 constructs of the invention are polynucleotide sequences encoding a polypeptide, wherein the polypeptide comprises at least one TREM2 or fragment thereof and a targeting moiety and optionally comprising a signal peptide and/or a purification moiety. The present invention also provides isolated polypeptides encoded by TREM2 constructs, vectors comprising TREM2 constructs, isolated cells comprising said vectors, and methods of use thereof.

Abstract: Among the various aspects of the present disclosure is the provision of methods of treating a microglial dysfunction-associated diseases, disorder, and conditions. The present disclosure provides for a method for treating microglial dysfunction in a subject having a microglial dysfunction-associated neurodegenerative disease comprising administering to a subject a therapeutically effective amount of a microglial rescuing agent. The present disclosure also provides for a method of reversing neuronal damage in a subject having a microglial dysfunction-associated neurodegenerative disease, wherein the microglial dysfunction-associated neurodegenerative disease is characterized by a single nucleotide polymorphisms (SNPs) or mutation in Trem2 or ApoE affecting microglial functions.

Abstract: Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-?. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

Abstract: Novel activating receptors of the lg super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-?. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

Abstract: Novel activating receptors of the lg super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-?. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

Abstract: An isolated and characterized monoclonal antibody (“440c”) prepared by immunizing Wistar/CRL rats subcutaneously with purified rat bone marrow IPC, fusing popliteal lymph nodes of the rats with SP2/0 myeloma spleen cells and differentially selecting for hybridome supernatants that successfully stain bone marrow derived IPC and fractions thereof using CD11c+ spleen cells and, differentially selecting for hybridoma supernatants from the CD11c+ spleen cells that successfully stain only CD 11 c+/Ly6c+/CD 11 b?/B220+ splenocytes to provide the monoclonal antibody.

Abstract: Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-?. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

Abstract: Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-?. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

Abstract: Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-?. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.

Abstract: A TREM-1 ligand is identified. This allows various derivatives to be provided/identified that are capable of binding to the TREM-1 receptor. The TREM-1 ligand or the derivatives can be used in screening for drugs/drug candidates. Substances that block or reduce binding of the TREM-1 ligand/derivative to a TREM-1 receptor may be useful for treating sepsis, particularly sepsis of bacterial or fungal origin. Antibodies to the ligand may be useful in diagnosing sepsis, particularly sepsis of bacterial or fungal origin.

Abstract: Novel activating receptors of the Ig super-family expressed on human myeloid cells, called TREM(s) (triggering receptor expressed on myeloid cells) are provided. Specifically, two (2) members of TREMs, TREM-1 and TREM-2 are disclosed. TREM-1 is a transmembrane glycoprotein expressed selectively on blood neutrophils and a subset of monocytes but not on lymphocytes and other cell types and is upregulated by bacterial and fungal products. Use of TREM-1 in treatment and diagnosis of various inflammatory diseases is also provided. TREM-2 is also a transmembrane glycoprotein expressed selectively on mast cells and peripheral dendritic cells (DCs) but not on granulocytes or monocytes. DC stimulation via TREM-2 leads to DC maturation and resistance to apoptosis, and induces strong upregulation of CCR7 and subsequent chemotaxis toward macrophage inflammatory protein 3-?. TREM-2 has utility in modulating host immune responses in various immune disorders, including autoimmune diseases and allergic disorders.