Comparison of dendritic cells obtained from autoimmunty-prone and resistant rats

Abstract

List of abbreviations AO -Albino Oxford; CDcluster of differentiation; CNS -central nervous system; DA -Dark Agouti; DCdendritic cells; EAE -experimental autoimmune encephalomyelitis; FCS -fetal calf serum; GM-CSF -granulocyte-macrophage colony-stimulating factor; iDCimmature DC; IFN -interferon; IL -interleukin; LNC -lymph node cells; LPSlipopolysaccharide; mDCmature DC; PBS -phosphate buffer saline; SD -standard deviation; Th -T helper; TNFtumor necrosis factor; tolDCtolerogenic DC. 4 Abstract Dendritic cells (DC) are responsible for the initiation and shaping of the adaptive immune response and are in the focus of autoimmunity research. We were interested in comparison of DC obtained from autoimmunity-prone Dark Agouti (DA) rats and autoimmunity-resistant Albino Oxford (AO) rats. DC were generated from bone marrow precursors and matured (mDC) by lipopolysaccharide. Tolerogenic DC (tolDC) obtained by vitamin D3 treatment were studied in parallel. Profile of cytokine production was different in AO and DA mDC and tolDC. Expression of MHC class II molecules and CD86 were higher in DA DC, while vitamin D3 reduced their expression in dendritic cells of both strains. Allogeneic proliferation of CD4 + T cells was reduced by AO tolDC, but not with DA tolDC in comparison to respective mDC. Finally, expression of various genes identified as differentially expressed in human mDC and tolDC was also analyzed in AO and DA DC. Again, AO and DA DC differed in the expression of the analyzed genes. To conclude, AO and DA DC differ in production of cytokines, expression of antigen presentation-related molecules and in regulation of CD4 + T proliferation. The difference is valuable for understanding the divergence of the strains in their susceptibility to autoimmunity.

Desmoglein-4 Deficiency Exacerbates Psoriasiform Dermatitis in Rats While Psoriasis Patients Displayed a Decreased Gene Expression of DSG4

“…In contrast to what has been in the mice model, our findings suggest that topical administration of IMQ in SD rats does not lead to spleen or lymph node enlargement. This could be due to different susceptibility to develop T cell-mediated diseases such as observed in experimental autoimmune encephalomyelitis or differences in DC response to IMQ between rodent strains ( 35 , 36 ). Similarly, OFA rats also showed no signs of spleen disorder despite exacerbated skin inflammation in response to IMQ suggesting that inflammatory events related to Dsg-4 deficiency may not reach distant tissues.…”

Optimal Tolerogenic Dendritic Cells in Type 1 Diabetes (T1D) Therapy: What Can We Learn From Non-obese Diabetic (NOD) Mouse Models?

“…The other spontaneous rodent model, the BB rat, displays a defect in thymic epithelial cells and severe lymphopeniea as well as altered maturation of DCs (1, 131, 132) and no preclinical testing of tolDCs seems to have been reported in this model. Very recently, a tolDCs and cDCs comparison was carried out in autoimmune-prone and resistant rats, but not in BB rats (133).…”