The present invention provides genetically modified non-human animals which are deficient in at least one or more types of CD3 genes selected from the group consisting of endogenous CD3, CD3, and CD3 in its genome and functionally express at least one or more types of human CD3 genes selected from the group consisting of human CD3, CD3, and CD3. In the genetically modified non-human animals of the present invention, mature T cell differentiation and production can take place, and immunocompetent cells including T cells can exert their functions. The genetically modified non-human animals of the present invention enable efficient evaluation and screening in the development of therapeutic agents and therapeutic methods that use human CD3-mediated targeted drugs.

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.

The invention concerns a non-human animal model useful for sensitively studying gene-gene interactions over a wide genetic background; methods for producing the animal model; and methods for studying gene-gene interactions using an animal model of the invention.

Herein is disclosed a method for differentiation of cells into insulin-producing cells, a cell population enriched for insulin-producing -cells and the use of such a cell population for treatment of a metabolic disorder in an individual in need thereof. Also disclosed is a method for treating a metabolic disorder.

The present invention relates to a pharmaceutical composition for treating and/or preventing arthritis, which comprising, as an active ingredient, a gene delivery vehicle into which an IK factor or a fragment thereof, or a nucleic acid encoding thereof is inserted. IK factor or the fragment thereof, and the nucleic acid encoding thereof, which are the active ingredient of the pharmaceutical composition according to the present invention, are derived from an organism and therefore, show no side effects in administered into a subject for a long time. Accordingly, they ensures safety and are expected to effectively treat arthritis by being involved in the upstream mechanism for suppressing arthritis.

A method for preparing pluripotent stem cell-derived hematopoietic stem cells and a method of constructing a humanized mouse model with the prepared hematopoietic stem cells. The method of preparing the hematopoietic stem cells identified an optimal differentiation condition according to a combination of low-molecular-weight compounds and protein growth factors without gene insertion, and thus may differentiate hematopoietic stem cells from pluripotent stem cells at high yield.

Methods of treating autoimmune diseases, such as vitiligo, by using compositions comprising DNA encoding a variant inducible heat shock protein 70 (HSP70i) having a mutation in the dendritic cell binding region thereof (HSP70i435-447) or an isolated variant gene product in the form of HSP70i with a modification in the dendritic cell activating region thereof (HSP70i435-447).

The present invention relates to a fusion proteins comprising regulatory T cell protein, VISTA (V-domain Immunoglobulin Suppressor of T cell Activation (PD-L3) and an immunoglobulin protein (Ig), preferably also containing a flexible linker intervening the VISTA and Ig Fc polypeptide. The invention also provides the use of VISTA polypeptides, multimeric VISTA polypeptides, VISTA-conjugates (e.g., VISTA-Ig), and VISTA antagonists for the treatment of autoimmune disease, allergy, and inflammatory conditions, especially lupus, multiple sclerosis, psoriasis, psoriatic arthritis, multiple sclerosis, Crohn's disease, inflammatory bowel disease and type 1 or type 2 diabetes.

The present invention relates to a fusion proteins comprising regulatory T cell protein, VISTA (V-domain Immunoglobulin Suppressor of T cell Activation (PD-L3) and an immunoglobulin protein (Ig), preferably also containing a flexible linker intervening the VISTA and Ig Fc polypeptide. The invention also provides the use of VISTA polypeptides, multimeric VISTA polypeptides, VISTA-conjugates (e.g., VISTA-Ig), and VISTA antagonists for the treatment of autoimmune disease, allergy, and inflammatory conditions, especially lupus, multiple sclerosis, psoriasis, psoriatic arthritis, multiple sclerosis, Crohn's disease, inflammatory bowel disease and type 1 or type 2 diabetes.

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.