(2010) found that CD4+ T cells recruited by astrocytes are essential for EAE onset. Therefore, we hypothesize that neutrophils in CNS from PAFR−/− mice may need signals provided by mononuclear cells (CD4+T cells) to promote tissue damage. Further studies are needed to define which signals may be influencing neutrophil-mediated tissue damage. Infiltrating cells synthesize molecules to recruit and activate HSP inhibitor clinical trial more cells to invade CNS tissue (Reboldi et al., 2009). It has been established that EAE-induced mice present elevated cytokines and chemokines levels

in CNS tissue at the peak of EAE (Fife et al., 2001, Juedes et al., 2000 and Ambrosini et al., 2003). We confirmed the presence of high levels of proinflammatory cytokines and chemokines in EAE-induced WT mice. However, PAFR−/− mice presented levels compared to control mice in all cytokines and chemokines measured, suggesting that infiltrating cells in these mice were not synthesizing these molecules. Lack of PAF receptor may be impairing IL-17 release by astrocytes, which were shown to be the source of this cytokine in the onset of EAE clinical signs (Kang

et al., 2010). In addition, lack of mononuclear cells in CNS tissue, which was shown by the diminished number AZD5363 cell line of CD4+ lymphocytes, may result in lower cytokine and chemokine synthesis. Kihara et al. (2005) found a decreased phagocytic activity in PAFR−/−macrophages. Our data suggest that the reduced amount of IL-17 and diminished number of CD4+ cells may account for the reduced phagocytic activity of macrophages lacking PAFR. Th17 response has been shown to be relevant in EAE (Langrish et al., 2005). To our knowledge, we showed, for the first

time, that this response may be impaired in EAE-induced PAFR−/− mice. The need for Th17 responses to induce EAE is still a matter of debate. While some studies consider it to be essential (Kroenke and Segal, 2007), others claim that it is not necessary (Kroenke, et al., 2010). We show here an association of diminished EAE severity and impaired Th17 response. In conclusion, we have shown that PAF receptor is important in the induction and development of EAE. Absence of this receptor leads to milder mononuclear cell infiltration, decrease of CD4+ Th17 lymphocytes and Exoribonuclease lower levels of inflammatory cytokines and chemokines in CNS tissue, but no influence on leukocyte rolling and adhesion. Female C57BL/6 mice were obtained from Animal Care Facilities of Federal University of Minas Gerais (UFMG, Brazil), aged between 9 and 10 weeks. Female PAFR−/− mice with the same age of C57BL/6 were a kind gift from professor Takao Shimizu (University of Tokyo) and were bred and maintained under SPF conditions at Instituto de Ciências Biológicas. The Animal Ethics Committee of UFMG approved all experimental procedures used (protocol number: 129/2006). EAE was induced using an emulsion containing myelin oligodendrocyte glycoprotein (MOG), Complete Freund’s Adjuvant (CFA) and attenuated Mycobacterium tuberculosis.