NBR1 (neighbor of BRCA1 gene 1) is a newly discovered signaling molecule containing a Phox and Bem1 (PB1) domain. PB1-domains are protein interaction modules. PB1 domain-containing molecules participate in diverse biological processes, which also include p62, Par-6, MEK5a, MEKK3, PKCζ and PKC λ/ι besides NBR1. We have recently reported that NBR1 regulates Th2 function and allergic airway inflammation. However, the role of NBR1 in the T cell development and in the regulation of other CD4+ T cell subsets remains to be elucidated. With the use of CD4+ T cell specific conditional NBR1-deficient mice, we found that NBR1 did not affect T cell development. Thymocyte subpopulations (double negative, double positive, CD4 or CD8 single positive cells) were similar between conditional NBR1-deficient mice and their WT littermates. CD4+ and CD8+ cells in the spleen and blood also did not differ significantly between these two groups. Furthermore, NBR1-deficiency did not affect the development of natural Treg in vivo and the differentiation of induced Treg in vitro. However, NBR1 was found selectively regulate Th2 function without affect Th1 cells. Interestingly, our preliminary data indicated that NBR1-deficiency might affect Th17 differentiation in vitro. These data suggest that NBR1 has no effect on T cell development, whereas it may selectively affect some CD4+ T cell subsets, especially Th2 and Th17. Further study is needed to elucidate the underlying mechanisms.
- Copyright © 2013 by The American Association of Immunologists, Inc.