CCDC88B is a novel regulator of maturation and effector functions of T cells during pathological inflammation.

James M Kennedy, Nassima Fodil, Sabrina Torre, Silayuv E Bongfen, Jean-Frédéric Olivier, Vicki Leung, David Langlais, Charles Meunier, Joanne Berghout, Pinky Langat, Jeremy Schwartzentruber, Jacek Majewski, Mark Lathrop, Silvia M Vidal, Philippe Gros

Index: J. Exp. Med. 211(13) , 2519-35, (2014)

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Abstract

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-γ 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. © 2014 Kennedy et al.