TY - JOUR
T1 - Altered lymphopoiesis and immunodeficiency in miR-142 null mice
AU - Kramer, Nicholas J.
AU - Wang, Wei Le
AU - Reyes, Estefany Y.
AU - Kumar, Bijender
AU - Chen, Ching Cheng
AU - Ramakrishna, Chandran
AU - Cantin, Edouard M.
AU - Vonderfecht, Steven L.
AU - Taganov, Konstantin D.
AU - Chau, Nelson
AU - Boldin, Mark P.
N1 - Publisher Copyright:
© 2015 by The American Society of Hematology.
PY - 2015/6/11
Y1 - 2015/6/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84931281751&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84931281751&partnerID=8YFLogxK
U2 - 10.1182/blood-2014-10-603951
DO - 10.1182/blood-2014-10-603951
M3 - Article
C2 - 25931583
AN - SCOPUS:84931281751
SN - 0006-4971
VL - 125
SP - 3720
EP - 3730
JO - Blood
JF - Blood
IS - 24
ER -