Cbfb in RORgt-regulated T cell function

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Zuoming  Sun
Organization: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
Fiscal Year: 2024
Award: $753,164
Funding agency: National Institute of Allergy and Infectious Diseases

Retinoid-related orphan receptor gamma t (RORyt) is a transcription factor that regulates the
differentiation of Th17 cells in the peripheral immune system and the development of
thymocytes in the central immune system. As pathogenic Th17 cells are responsible for tissue
damages associated with many types of autoimmune diseases including multiple sclerosis,
psoriasis and inflammatory bowel disease, there is a medical need for the development of
RORyt-based therapies to treat these autoimmune diseases. However, inhibition of RORyt, that
ameliorates Th17-mediated autoimmune diseases, also disrupts thymocyte development and
thus prevents the replenishment of the peripheral immune system with T cells critical for
clearance of infection by pathogens such as bacteria and virus. Further, inhibition of RORyt
activity could lead to the development of cancer. We thus propose to separate RORyt function in
Th17 cells and thymocytes by characterizing its shared and unique co-factors in these two types
of cells, which will facilitate to achieve the long-term goal of development of RORyt-based
therapies for treatment of autoimmune disease with minimum toxic side effects.

Terms: <Anti-Oncogenes><Antioncogenes><Autoimmune Diseases><Autoimmune Status><Autoimmunity><Bacteria><Basal Transcription Factor><Basal transcription factor genes><Body Tissues><CBF-Beta Gene><CBFB><CBFB gene><CTLA-8><CTLA-8 Gene><CTLA8><CTLA8 Gene><Cancer Genes><Cancer Suppressor Genes><Cancer-Promoting Gene><Cancers><Cell Body><Cell Compartmentation><Cell Compartmentations><Cell Function><Cell Physiology><Cell Process><Cells><Cellular Function><Cellular Physiology><Cellular Process><Collaborations><Core-Binding Factor, Beta Subunit><Cytotoxic T-Lymphocyte-Associated Antigen 8><Cytotoxic T-Lymphocyte-Associated Antigen 8 Gene><Cytotoxic T-Lymphocyte-Associated Serine Esterase 8><Cytotoxic T-Lymphocyte-Associated Serine Esterase 8 Gene><Development><Disseminated Sclerosis><EAE><Emerogenes><Experimental Allergic Encephalitis><Experimental Allergic Encephalomyelitis><Experimental Autoimmune Encephalitis><Experimental Autoimmune Encephalomyelitis><Gene Deletion><Gene Expression><Gene Transcription><General Transcription Factor Gene><General Transcription Factors><Generations><Genetic Transcription><Germinoblastic Sarcoma><Germinoblastoma><Goals><IL-17><IL-17 Gene><IL-17A><IL-17A Gene><IL17><IL17 Protein><IL17 gene><IL17A><IL17A Gene><Immune response><Immune system><Immunity><Immunological response><Infection><Inflammatory Bowel Diseases><Inflammatory Bowel Disorder><Interleukin 17 (Cytotoxic T-Lymphocyte-Associated Serine Esterase 8)><Interleukin 17 (Cytotoxic T-Lymphocyte-Associated Serine Esterase 8) Gene><Interleukin 17 Precursor><Interleukin 17 Precursor Gene><Interleukin-17><Lymphoma><Lymphomagenesis><Malignant Lymphoma><Malignant Neoplasms><Malignant Tumor><Mediating><Medical><Mice><Mice Mammals><Mouse Strains><Multiple Sclerosis><Murine><Mus><Onco-Suppressor Genes><Oncogenes><Oncogenes-Tumor Suppressors><Orphan><PEBP2B><Pathogenicity><Pathologic><Peripheral><Polyomavirus Enhancer-Binding Protein 2-Beta><Psoriasis><RNA Expression><Reagent><Receptor Inhibition><Receptor Protein><Recessive Oncogenes><Records><Reticulolymphosarcoma><Retinoic Acid Agent><Retinoic Acid and Derivatives><Retinoids><Subcellular Process><T-Cell Development><T-Cell Ontogeny><T-Cells><T-Lymphocyte><T-Lymphocyte Development><Therapeutic><Thymic Lymphoma><Thymocyte Development><Thymus Lymphoma><Tissues><Transcription><Transcription Factor Proto-Oncogene><Transcription factor genes><Transforming Genes><Tumor Suppressing Genes><Tumor Suppressor Genes><Virus><Work><autoimmune condition><autoimmune disorder><autoimmune encephalomyelitis><autoimmunity disease><cell type><cofactor><developmental><gene deletion mutation><gene function><host response><immune system response><immunoresponse><in vivo><inflammatory disease of the intestine><inflammatory disorder of the intestine><inhibitor><innovate><innovation><innovative><insular sclerosis><intestinal autoinflammation><malignancy><mutant><neoplasm/cancer><novel><oncosuppressor gene><pathogen><pharmacologic><prevent><preventing><programs><psoriasiform><psoriatic><receptor><receptor binding><receptor bound><receptor function><recruit><side effect><skills><success><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><thymocyte><thymus derived lymphocyte><transcription factor>