Abstract: The present application relates to compositions and methods for tracing cell networks, e.g., for investigation of cell interactions in the CNS with single cell resolution.

Abstract: Described herein are microbial probiotics that, in response to metabolite extracellular ATP (eATP) produced in the microenvironment of inflamed tissues detected, e.g., via an engineered mammalian P2Y2 receptor, secrete an anti-inflammatory protein, e.g., IL-2, IL-10, or the CD39-like eATP-degrading enzyme apyrase. Thus, provided herein is an isolated Saccharomyces cell (or cells, e.g., a population of such cells) that has been engineered to express one, two, or all three exogenous proteins selected from: (I) a mammalian P2Y purinoceptor 2 (P2Y2) protein, preferably human P2Y2; 15 (ii) a mutant Gpa1 protein comprising at least 5 C-terminal residues from a mammalian G alpha, preferably Gai3, wherein the mutant Gpa1 protein couples the P2Y2 protein to the yeast mating pathway; and (iii) an anti-inflammatory protein.

Abstract: Methods for identifying compounds that modulate the generation of regulatory T cells (Treg) in vivo and in vitro, i.e., compounds that act on the transcription factors that increase or decrease expression of Foxp3.

Abstract: Embodiments of various aspects described herein are directed to methods and compositions for producing a tolerogenic or immunosuppressive dendritic cell. In particular, an immunosuppressive dendritic cell can be produced by contacting a dendritic cell with an agent that stimulates the IL-27/ectonucleotidase CD39 axis signaling. In some embodiments, the methods and/or compositions described herein can be used for treating an autoimmune disease or disorder, e.g., but not limited to multiple sclerosis (MS) and type 1 diabetes.

Abstract: Methods for treating, or reducing risk of developing, seasonal worsening of multiple sclerosis (MS) in a subject who has MS, comprising administering a melatonin agonist to a subject.

Abstract: Embodiments of various aspects described herein are directed to methods and compositions for producing a tolerognic or immunosuppressive dendritic cell. In particular, an immunosuppressive dendritic cell can be produced by contacting a dendritic cell with an agent that stimulates the IL 27/ectonucleotidase CD39 axis signaling. In some embodiments, the methods and/or compositions described herein can be used for treating an autoimmune disease or disorder, e.g., but not limited to multiple sclerosis (MS) and type 1 diabetes.

Abstract: A method of treating a T cell-mediated inflammatory autoimmune disease by administering to an individual in need thereof an immunogenic composition comprising a recombinant construct of a nucleic acid sequence encoding heat shock protein 90 (HSP 90), or an active fragment thereof, wherein the nucleic acid sequence is operatively linked to one or more transcription control sequences. The disease is other than insulin dependent diabetes mellitus (IDDM) or rheumatoid arthritis. The administering of the immunogenic composition results in a shift of the immune response to a Th2 response, thereby treating the disease.

Abstract: A method of treating a T cell-mediated inflammatory autoimmune disease by administering to an individual in need thereof an immunogenic composition comprising a recombinant construct of a nucleic acid sequence encoding heat shock protein 90 (HSP 90), or an active fragment thereof, wherein the nucleic acid sequence is operatively linked to one or more transcription control sequences. The disease is other than insulin dependent diabetes mellitus (IDDM) or rheumatoid arthritis. The administering of the immunogenic composition results in a shift of the immune response to a Th2 response, thereby treating the disease.

Abstract: A method of treating a T cell-mediated inflammatory autoimmune disease by administering to an individual in need thereof an immunogenic composition comprising a recombinant construct of a nucleic acid sequence encoding heat shock protein 90 (HSP 90), or an active fragment thereof, wherein the nucleic acid sequence is operatively linked to one or more transcription control sequences. The disease is other than insulin dependent diabetes mellitus (IDDM) or rheumatoid arthritis. The administering of the immunogenic composition results in a shift of the immune response to a Th2 response, thereby treating the disease.

Abstract: Methods for identifying compounds that modulate the generation of regulatory T cells (Treg) in vivo and in vitro, i.e., compounds that act on the transcription factors that increase or decrease expression of Foxp3.

Abstract: As described herein, lactosylceramide (LacCer) levels are up-regulated in the CNS during chronic experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). LacCer acts in an autocrine manner to trigger transcriptional programs that promote the recruitment and activation of CNS infiltrating monocytes and microglia, and neurodegeneration. In addition, increased B4GALT6 expression and LacCer levels were detected in CNS MS lesions in human patients. Finally, the inhibition of LacCer synthesis suppressed local CNS innate immunity and neurodegeneration in EAE, and interfered with the activation of human astrocytes in vitro. Thus, B4GALT6 is a therapeutic target for MS and other neuroinflammatory disorders.

Abstract: Methods and compositions for increasing the number and/or activity of regulatory T cells (Tregs) in vivo and in vitro, to induce tolerance to diabetogenic autoantigens.

Abstract: Methods for increasing the numbers of regulatory T cells (Treg), e.g., in a population of T cells or in a patient.

Abstract: Methods for treating, or reducing risk of developing, seasonal worsening of multiple sclerosis (MS) in a subject who has MS, comprising administering a melatonin agonist to a subject.

Abstract: A method of treating a T cell-mediated inflammatory autoimmune disease by administering to an individual in need thereof an immunogenic composition comprising a recombinant construct of a nucleic acid sequence encoding heat shock protein 90 (HSP 90), or an active fragment thereof, wherein the nucleic acid sequence is operatively linked to one or more transcription control sequences. The disease is other than insulin dependent diabetes mellitus (IDDM) or rheumatoid arthritis. The administering of the immunogenic composition results in a shift of the immune response to a Th2 response, thereby treating the disease.

Abstract: As described herein, lactosylceramide (LacCer) levels are up-regulated in the CNS during chronic experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). LacCer acts in an autocrine manner to trigger transcriptional programs that promote the recruitment and activation of CNS infiltrating monocytes and microglia, and neurodegeneration. In addition, increased B4GALT6 expression and LacCer levels were detected in CNS MS lesions in human patients. Finally, the inhibition of LacCer synthesis suppressed local CNS innate immunity and neurodegeneration in EAE, and interfered with the activation of human astrocytes in vitro. Thus, B4GALT6 is a therapeutic target for MS and other neuroinflammatory disorders.

Abstract: A method of treating a T cell-mediated inflammatory autoimmune disease by administering to an individual in need thereof an immunogenic composition comprising a recombinant construct of a nucleic acid sequence encoding heat shock protein 90 (HSP 90), or an active fragment thereof, wherein the nucleic acid sequence is operatively linked to one or more transcription control sequences. The disease is other than insulin dependent diabetes mellitus (IDDM) or rheumatoid arthritis. The administering of the immunogenic composition results in a shift of the immune response to a Th2 response, thereby treating the disease.

Abstract: Embodiments of various aspects described herein are directed to methods and compositions for producing a tolerogenic or immunosuppressive dendritic cell. In particular, an immunosuppressive dendritic cell can be produced by contacting a dendritic cell with an agent that stimulates the IL 27/ectonucleotidase CD39 axis signaling. In some embodiments, the methods and/or compositions described herein can be used for treating an autoimmune disease or disorder, e.g., but not limited to multiple sclerosis (MS) and type 1 diabetes.

Abstract: The present invention relates to methods and kits for diagnosing multiple sclerosis (MS) in a subject. Particularly, the present invention relates to methods and kits for diagnosing a subtype of MS in a subject, the subtype selected from relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS) and a pathologic sub-type of MS lesions selected from Pattern I and Pattern II MS lesion.

Abstract: A method of treating a T cell-mediated inflammatory autoimmune disease by administering to an individual in need thereof an immunogenic composition comprising a recombinant construct of a nucleic acid sequence encoding heat shock protein 90 (HSP 90), or an active fragment thereof, wherein the nucleic acid sequence is operatively linked to one or more transcription control sequences. The disease is other than insulin dependent diabetes mellitus (IDDM) or rheumatoid arthritis. The administering of the immunogenic composition results in a shift of the immune response to a Th2 response, thereby treating the disease.