Mohammad G. Mohammad, Vicky W.W. Tsai, Samuel N. Breit, Paul E. Sawchenko and David A. Brown
Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Sharjah, Sharjah, UAE
CCAAT/enhancer binding protein delta (CEBPD), a bZIP-transcription factor, is an emerging regulator of innate immune responses and therefore might influence adaptive immune responses. However, it hasn't been examined in the context of central nervous system (CNS) inflammation and T-cell activation. This study aimed to determine the role of CEBPD in experimental autoimmune encephalomylitis (EAE) a T-cell mediated CNS autoimmune disease. CEBPD was upregulated at the protein and RNA level in peripherally derived DCs and astrocytes in the EAE affected CNS and animals lacking CEBPD had significantly less disease. Follow on BM chimeric experiments showed that it was CEBPD expression in peripherally derived immune cells that mediated differences in EAE severity. To identify cells other than DCs that expressed CEBPD throughout disease we developed an intracellular staining method to detect CEBPD protein expression. There was no CEBPD expression in peripherally derived CNS immune cells, other than in DCs. To detect functional changes in DC activity we examined Th-lymphocytes phenotype throughout the course of EAE and showed a significant reduction in Th17: Treg ratio when DC CEBPD was missing. The same was observed in an in vitro model of T-cell development directed by DCs that lacked CEBPD. These DCs also had significantly increased IL10 mRNA expression. Further, blocking IL-10 signaling completely compensated for the lack of CEBPD expression in DCs both in vitro and in vivo. These studies identify CEBPD as an important DC factor in regulating inflammatory response through directing T-lymphocyte development and promoting autoimmunity.