| First Author | Kennedy JM | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 13 | Pages | 2519-35 |
| PubMed ID | 25403443 | Mgi Jnum | J:230618 |
| Mgi Id | MGI:5763360 | Doi | 10.1084/jem.20140455 |
| Citation | Kennedy JM, et al. (2014) CCDC88B is a novel regulator of maturation and effector functions of T cells during pathological inflammation. J Exp Med 211(13):2519-35 |
| abstractText | We used a genome-wide screen in mutagenized mice to identify genes which inactivation protects against lethal neuroinflammation during experimental cerebral malaria (ECM). We identified an ECM-protective mutation in coiled-coil domain containing protein 88b (Ccdc88b), a poorly annotated gene that is found expressed specifically in spleen, bone marrow, lymph nodes, and thymus. The CCDC88B protein is abundantly expressed in immune cells, including both CD4(+) and CD8(+) T lymphocytes, and in myeloid cells, and loss of CCDC88B protein expression has pleiotropic effects on T lymphocyte functions, including impaired maturation in vivo, significantly reduced activation, reduced cell division as well as impaired cytokine production (IFN-gamma and TNF) in response to T cell receptor engagement, or to nonspecific stimuli in vitro, and during the course of P. berghei infection in vivo. This identifies CCDC88B as a novel and important regulator of T cell function. The human CCDC88B gene maps to the 11q13 locus that is associated with susceptibility to several inflammatory and auto-immune disorders. Our findings strongly suggest that CCDC88B is the morbid gene underlying the pleiotropic effect of the 11q13 locus on inflammation. |
