The present invention provides a non-human animal having human interleukin-34 (IL-34) in the body thereof; a method for producing a non-human animal having human microglia, which includes transplanting human CD34-positive hematopoietic stem cells into the non-human animal having human IL-34 in the body; and a method for producing human microglia, which includes obtaining human microglia from the non-human animal having human microglia.

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

The present invention relates to methods of immune modulation. In particular, the present invention relates to regulation of inflammation and immune responses by modulation of ABCF1. Modulation of ABCF1 may be useful in the treatment of sepsis, autoimmune diseases, cancer or infections.

Genetically modified non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome are provided. Also provided are methods for making non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome, and methods for using non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human T cell and/or natural killer (NK) cell development and function, in modeling human pathogen infection of human T cells and/or NK cells, and in various in vivo screens.

The present invention relates to: a method for screening an antifungal agent, the method measuring the amount or activity of proteins involved in passage through the brain-blood barrier; a biomarker composition for diagnosing meningoencephalitis or cryptococcosis; a diagnostic kit including said composition; and a therapeutic pharmaceutical composition including an inhibitor for the protein.

This disclosure provides peptides which have a strong affinity for the checkpoint receptor “programmed death 1” (PD-1). These peptides block the interaction of PD-1 with its ligand PD-L1 and can therefore be used for various therapeutic purposes, such as inhibiting the progression of a hyperproliferative disorder, including cancer; treating infectious diseases; enhancing a response to vaccination; treating sepsis; and promoting hair re-pigmentation or lightening of pigmented skin lesions.

Provided herein are multivalent particles and compositions of multivalent particles for blocking viral infection.

The present invention provides a non-human animal having human interleukin-34 (IL-34) in the body thereof; a method for producing a non-human animal having human microglia, which includes transplanting human CD34-positive hematopoietic stem cells into the non-human animal having human IL-34 in the body; and a method for producing human microglia, which includes obtaining human microglia from the non-human animal having human microglia.

The present invention relates to cells engineered to express at least one cytokine and at least one antigen which induces the self differentiation of dendritic cell (DC) progenitor cells into functional antigen-presenting induced DC (iDC). Moreover, therapeutic uses of said iDC for regenerating the immune system after transplantation of hematopoietic stem cells are disclosed. Said iDC are also useful for generating mice with a functional endogenously regenerated humanized immune system producing antigen-specific T and B cell responses which can be used as animal models for the study of the human adaptive immune responses.

An interleukin which binds to IL-2 receptor (IL-2R), or a nucleotide sequence encoding therefor, wherein the interleukin or nucleotide sequence is adapted to be targeted to the liver.