Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized B-cell activating factor gene. Non-human animals and cells that express a human or humanized B-cell activating factor protein from an endogenous B-cell activating factor locus are described.

The invention is a simplified model on kidney rejection in animals and its setting approach. The method involves isolating dendritic cells from male mice and isolating T cells from female mice and then using the naive T cells in vitro to culture concurrently with male dendritic cells. Those activated T cells from female origin were injected into renal cortex in male mice for the purpose of attacking renal cortex. The animal model simulates the renal transplant rejection method to enable effective induction of renal transplant immune reaction.

The present invention is based, in part, on the identification of methods of modulating PD-1 expression and/or activity in regulatory T cells (Tregs) to thereby regulate effector immune responses in effector T cells (Teffs).

The present inventors provide HER3 vaccine vector compositions and methods of using the same. More specifically, the present inventors demonstrate, in part, that a combination of HER3 vaccine vectors with checkpoint inhibitors suppresses or eliminates cancer cells more effectively than either alone.

It was found that bacteria belonging to the genus Clostridium induce accumulation of regulatory T cells (Treg cells) in the colon. Moreover, the present inventors found that regulatory T cells (Treg cells) induced by from these bacteria suppressed proliferation of effector T-cells. From these findings, the present inventors found that the use of bacteria belonging to the genus Clostridium or a physiologically active substance derived therefrom made it possible to induce proliferation or accumulation of regulatory T cells (Treg cells), and further to suppress immune functions.

It was found that bacteria belonging to the genus Clostridium induce accumulation of regulatory T cells (Treg cells) in the colon. Moreover, the present inventors found that regulatory T cells (Treg cells) induced by from these bacteria suppressed proliferation of effector T-cells. From these findings, the present inventors found that the use of bacteria belonging to the genus Clostridium or a physiologically active substance derived therefrom made it possible to induce proliferation or accumulation of regulatory T cells (Treg cells), and further to suppress immune functions.

Methods of preventing or treating rheumatoid arthritis (RA) in a subject by introducing the DRB1*04:01.sup.K71E mutation that is resistant to RA. The resistant allele is introduced into the subject having or at risk of developing RA, using a HLA CRISPR/Cas9 vector that targets codon 71 in the HLA allele DRB1*04:01, introducing a single A to G point mutation in codon 71 by homology directed repair to alter the lysine at position 71 of the expressed protein to glutamic acid. This modified allele is affected in the subject's hematopoietic stem cells, which are then expanded and transplanted back into the patient. This microgene therapy confers RA-resistance via an autologous transplant. The invention includes isolated nucleic acids, vectors, recombinant viruses, cells, and pharmaceutical compositions to modify the HLA DRB1*04:01 allele.

The present invention provides a composition which comprises the following Thyroid Stimulating Hormone Recept or (TSHR) peptides: (i) all or part of the amino acid sequence KKKKYVSIDVTLQQLESHKKK (SEQ ID NO: 1), or a part thereof, or a sequence having at least 60% sequence identity to SEQ ID NO:1; and (ii) all or part of the amino acid sequence GLKMFPDLTKVYSTD (SEQ ID NO: 2), or a part thereof, or a sequence having at least 60% sequence identity to SEQ ID NO:2. The present invention also relates to the use of such a composition for the prevention or suppression of activating autoantibody formation in Graves' disease.

The present invention relates to an autoimmune disease animal model and a method for preparing the same. The animal model of the present invention efficiently generates an autoantibody that causes autoimmune disease, by introducing an autoantigen-encoding gene through the Cre-LoxP system, which enables stable and continuous expression of the autoantigen at a desired time by treatment of Cre recombinase. Contrary to the conventional method that fails to effectively produce autoantibody due to leaky expression and immune tolerance, or requires repeated administration over several weeks, the present invention achieves sustainable expression of an effective amount of autoantigen by only one TAT-Cre recombinase treatment, thus may be utilized as an outstanding animal model reproducing various symptoms and molecular mechanisms of autoimmune diseases.

Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized B-cell activating factor gene. Non-human animals and cells that express a human or humanized B-cell activating factor protein from an endogenous B-cell activating factor locus are described.