Altered lymphopoiesis and immunodeficiency in miR-142 null mice
| Autor: | Estefany Y. Reyes, Chandran Ramakrishna, Ching-Cheng Chen, Bijender Kumar, Nicholas J. Kramer, Nelson Chau, Edouard M. Cantin, Konstantin D. Taganov, Steven Vonderfecht, Mark Boldin, Wei-Le Wang |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Immunology Biology Biochemistry Gene Knockout Techniques Mice Immune system Antigen medicine Animals Lymphopoiesis B-cell activating factor Immunodeficiency Regulation of gene expression B-Lymphocytes Immunity Cellular Immunologic Deficiency Syndromes Cell Biology Hematology medicine.disease Immunity Humoral Cell biology Mice Inbred C57BL MicroRNAs Haematopoiesis Gene Expression Regulation Primary immunodeficiency Female Gene Deletion B-Cell Activation Factor Receptor Immunoproliferative Disorders |
| Zdroj: | Blood. 125:3720-3730 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | MicroRNAs (miRNAs) are a class of powerful posttranscriptional regulators implicated in the control of diverse biological processes, including regulation of hematopoiesis and the immune response. To define the biological functions of miR-142, which is preferentially and abundantly expressed in immune cells, we created a mouse line with a targeted deletion of this gene. Our analysis of miR-142(-/-) mice revealed a critical role for this miRNA in the development and homeostasis of lymphocytes. Marginal zone B cells expand in the knockout spleen, whereas the number of T and B1 B cells in the periphery is reduced. Abnormal development of hematopoietic lineages in miR-142(-/-) animals is accompanied by a profound immunodeficiency, manifested by hypoimmunoglobulinemia and failure to mount a productive immune response to soluble antigens and virus. miR-142(-/-) B cells express elevated levels of B-cell-activating factor (BAFF) receptor (BAFF-R) and as a result proliferate more robustly in response to BAFF stimulation. Lowering the BAFF-R gene dose in miR-142(-/-) mice rescues the B-cell expansion defect, suggesting that BAFF-R is a bona fide miR-142 target through which it controls B-cell homeostasis. Collectively, our results uncover miR-142 as an essential regulator of lymphopoiesis, and suggest that lesions in this miRNA gene may lead to primary immunodeficiency. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|