To identify a microorganism causing the development of primary sclerosing cholangitis associated with ulcerative colitis. A Klebsiella pneumoniae strain inducing inflammation in the liver.

The present invention relates to an in vitro immune synapse system and a method of in vitro evaluating immune response using the same. The in vitro immune synapse system includes antigen-presenting cells (APCs) and at least one cell type of several specific T cell subtypes isolated from peripheral blood mononuclear cells (PBMCs), all of which is from a same individual of pigs. When a test sample is co-cultured in the in vitro immune synapse system for a given period, it can be determined that the test sample is immunogenic, immunostimulatory or not according to the immunization-related changes of these cells, thereby potentially replacing some kinds of animal experimentation.

The present invention describes combination treatment comprising a PD-1 axis binding antagonist and an agent that decreases or inhibits TIGIT expression and/or activity and methods for use thereof, including methods of treating conditions where enhanced immunogenicity is desired such as increasing tumor immunogenicity for the treatment of cancer or chronic infection.

The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I polypeptide and/or human or humanized 2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/B1N, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdc.sup.scid IL2re.sup.tmlWjl/SzJ (NSG), NOD.Cg-Rag1.sup.tm1Mom Il2rg.sup.tmlWjl/SzJ (NRG) and NOD.Cg-Prkdc.sup.scid Il2rg.sup.tm1Sug/JicTac (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice. Methods for assessment of therapeutic antibodies or putative therapeutic antibodies in the genetically modified immunodeficient mice characterized by an intact complement system are provided according to specific aspects of the present invention.

The present invention provides a non-human animal in which a DNA comprising an hp7 sequence-encoding DNA and a poly A addition signal-encoding DNA added on the 3 side of a DNA encoding an arbitrary foreign gene is inserted in the same reading frame as that of an arbitrary target gene present on the genome of the non-human animal.

Described herein are methods and compositions for producing modified, PD-L1 expressing hematopoietic stem cells, and uses thereof. Aspects of the invention relate to modulating the expression of micro RNA that controls the expression of PD-L1 in the hematopoietic stem cell. Methods for modulating the expression of micro RNA include, e.g., introducing to the cell a nucleic acid encoding a given micro RNA, or an agent that inhibits a given micro RNA.

The present disclosure relates to a JAK3 gene-mutated severe combined immunodeficiency animal model and a method of constructing the same. In the JAK3 gene-mutated severe combined immunodeficiency animal model of the present disclosure, the JAK3 gene is specifically deficient, the expression of cytokines is regulated by controlling the number and activity of macrophages, and the thymus, lymphocytes, and Peyer's patches, which are observed in conventional severe combined immunodeficiency animal models, particularly mini-pigs, are completely lacking. In addition, the animal model of the present disclosure can be used as a treatment model for JAK3 SCID patients, as similar phenotypes are observed in patients with human severe combined immunodeficiency caused by a JAK3 gene mutation, and can be used for artificial blood development or xenotransplantation.

The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I polypeptide and/or human or humanized 2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

Genetically modified mice and methods and compositions for making and using the same are provided, wherein the genetic modification comprises humanization of an FcRI protein.