| First Author | Kawai Y | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 10 | Pages | 4075-80 |
| PubMed ID | 21325057 | Mgi Jnum | J:170477 |
| Mgi Id | MGI:4946557 | Doi | 10.1073/pnas.1014178108 |
| Citation | Kawai Y, et al. (2011) Claudin-4 induction by E-protein activity in later stages of CD4/8 double-positive thymocytes to increase positive selection efficiency. Proc Natl Acad Sci U S A 108(10):4075-80 |
| abstractText | Claudins (Clds) are crucial constituents of tight-junction strands in epithelial cells and have a central role in barrier functions. We show that Cld4 is unexpectedly expressed in normal thymic lymphocytes independently of tight junctions. The Cld4 expression was mostly confined to a portion of the CD4/CD8 double-positive (DP) cells. The proportion of Cld4(+) DP cells was markedly increased in MHC-I(-/-) II(-/-) mice but decreased in Rorgamma(-/-) mice, and Cld4(+) DP cells contained higher levels of the rearranged Tcra transcripts involving the most distal Va and Ja segments than Cld4(-) DP cells. The Cld4 expression levels were reduced in E47-deficient mice in a gene dose-dependent manner, and ChIP analysis indicated that E2A and HEB were bound to the E-box sites of the putative Cldn4 promoter region. Functionally, Cld4 showed a potent T-cell receptor costimulatory activity by coligation with CD3. The Cld4 was distributed diffusely on the cell surface and associated with CD4/lck independently of CD3 in the resting thymocytes. However, Cld4 was strongly recruited to the immunological synapse on specific T-cell receptor engagement through antigen-presenting cells. In the fetal thymic organ culture, knockdown of Cldn4 resulted in the reduced generation of CD4/CD8 single-positive cells from the DP cells. These results suggest that Cld4 is induced by E-protein activity in the later stages of DP cells to increase the efficiency of positive selection, uncovering a hitherto unrecognized function of a Cld family protein. |
