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J Exp Med. 2010 Oct 25;207(11):2521-32. doi: 10.1084/jem.20092759. Epub 2010 Oct 11.

Tbata modulates thymic stromal cell proliferation and thymus function.

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Experimental Transplantation Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.


Niche availability provided by stromal cells is critical to thymus function. Thymi with diminished function contain fewer stromal cells, whereas thymi with robust function contain proliferating stromal cell populations. Here, we show that the thymus, brain, and testes-associated gene (Tbata; also known as SPATIAL) regulates thymic epithelial cell (TEC) proliferation and thymus size. Tbata is expressed in thymic stromal cells and interacts with the enzyme Uba3, thereby inhibiting the Nedd8 pathway and cell proliferation. Thymi from aged Tbata-deficient mice are larger and contain more dividing TECs than wild-type littermate controls. In addition, thymic reconstitution after bone marrow transplantation occurred more rapidly in Rag2(-/-)Tbata(-/-) mice than in Rag2(-/-)Tbata(+/+) littermate controls. These findings suggest that Tbata modulates thymus function by regulating stromal cell proliferation via the Nedd8 pathway.

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