| First Author | Podojil JR | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 3 | Pages | 897-907 |
| PubMed ID | 29898965 | Mgi Jnum | J:264318 |
| Mgi Id | MGI:6195412 | Doi | 10.4049/jimmunol.1700811 |
| Citation | Podojil JR, et al. (2018) B7-H4 Modulates Regulatory CD4(+) T Cell Induction and Function via Ligation of a Semaphorin 3a/Plexin A4/Neuropilin-1 Complex. J Immunol 201(3):897-907 |
| abstractText | The potent immune regulatory function of an agonistic B7-H4-Ig fusion protein (B7-H4Ig) has been demonstrated in multiple experimental autoimmune models; however, the identity of a functional B7-H4 receptor remained unknown. The biological activity of B7-H4 is associated with decreased inflammatory CD4(+) T cell responses as supported by a correlation between B7-H4-expressing tumor-associated macrophages and Foxp3(+) T cells within the tumor microenvironment. Recent data indicate that members of the semaphorin (Sema)/plexin/neuropilin (Nrp) family of proteins both positively and negatively modulate immune cell function. In this study, we show that B7-H4 binds the soluble Sema family member Sema3a. Additionally, B7-H4Ig-induced inhibition of inflammatory CD4(+) T cell responses is lost in both Sema3a functional mutant mice and mice lacking Nrp-1 expression in Foxp3(+) T cells. These findings indicate that B7-H4Ig binds to Sema3a, which acts as a functional bridge to stimulate an Nrp-1/Plexin A4 heterodimer to form a functional immunoregulatory receptor complex resulting in increased levels of phosphorylated PTEN and enhanced regulatory CD4(+) T cell number and function. |
