CD4− CD8α+ CD11b− DCs (CD8+
cDCs) are localized in the T-cell zone and specialize in MHC class I presentation. JNK inhibitor CD4− CD8 α− CD11b+ DCs have also been identified and are called DN cDCs.[9, 32] All three subtypes of DCs were significantly increased in the spleens from Fli-1∆CTA/∆CTA mice compared with wild-type controls. On the other hand, Fli-1∆CTA/∆CTA B6 mice had increased pre-cDCs and monocyte populations in PBMCs compared with wild-type littermates (Fig. 3). Despite the significant increase of macrophage and DC populations in spleens from Fli-1ΔCTA/ΔCTA mice, these mice did not show any phenotypic pathology. There were also no pathological changes in bone marrow from Fli-1ΔCTA/ΔCTA mice. The pDC population in the spleens from Fli-1∆CTA/∆CTA mice was significantly increased when compared with wild-type
littermates (Fig. 2). The pDCs are strong producers of type I interferon, and type I interferon signature is linked to development of learn more systemic lupus erythematosus.[1, 6] Expression of Fli-1 is implicated in lupus disease development in both human patients and animal models of lupus.[25-27] However, the interferon level in the serum is not detectable from Fli-1ΔCTA/ΔCTA mice (data not shown). It is interesting to note that Fli-1∆CTA/∆CTA mice had significantly increased pDCs in the spleen but not in PBMCs, expression levels of MHC on pDCs in the spleens from Fli-1ΔCTA/ΔCTA mice were similar compared with those from wild-type Lonafarnib nmr mice. Further study is needed to address this difference. We have found that the pre-cDC populations in BM from Fli-1ΔCTA/ΔCTA mice were not significantly different compared with that from wild-type mice, however, both the cDC and pre-cDC populations in spleens from Fli-1ΔCTA/ΔCTA mice were higher compared with wild-type controls (Figs 1 and 2). We do not know the mechanisms that result in the increase in the pre-cDC population in the spleen of
Fli-1ΔCTA/ΔCTA mice, one possibility may be a change in the migration of pre-cDCs in Fli-1ΔCTA/ΔCTA mice and more pre-cDCs are actively attracted into the spleen in these mice. The increase in cDC populations in spleen suggests that pre-cDC cells may mature in lymphoid tissues like the spleen, outside the bone marrow. Several studies have demonstrated that stromal cells play an important role in immune cell development and that gene-deficient stromal cells affect normal immune cell development.[33, 34] Our bone marrow transplantation study clearly demonstrated that the expression of Fli-1 in both HSCs and stromal cells affects mononuclear phagocyte development. We found that Fli-1∆CTA/∆CTA B6 mice receiving BM cells from wild-type B6 mice (WF) had a significantly increased population of monocytes in PBMCs when compared with wild-type B6 mice receiving BM from wild-type B6 mice (WW).