Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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! # Ola via Alexandros G.Sfakianakis on Inoreader

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Δευτέρα 19 Νοεμβρίου 2018

Fc{gamma}RIIb on B Cells and Myeloid Cells Modulates B Cell Activation and Autoantibody Responses via Different but Synergistic Pathways in Lupus-Prone Yaa Mice [AUTOIMMUNITY]

C57BL/6 (B6).FcRIIb–/–.Yaa mice spontaneously develop lethal lupus nephritis. To define the cell type–specific role of FcRIIb in Yaa-associated lupus, we established B cell– (CD19Cre.Yaa), myeloid cell– (C/EBPαCre.Yaa), and dendritic cell– (DC) (CD11cCre.Yaa) specific FcRIIb-deficient B6.Yaa mouse strains. CD19Cre.Yaa mice developed milder lupus than B6.FcRIIb–/–.Yaa mice, indicating that FcRIIb deficiency on B cells is not sufficient for the development of severe disease. Surprisingly, C/EBPαCre.Yaa mice also showed autoantibody production and mild lupus similar to that in CD19Cre.Yaa mice, whereas CD11cCre.Yaa mice stayed disease free. These observations indicate that FcRIIb deficiency in B cells and myeloid cells, but not DCs, contributes to the severe disease in B6.FcRIIb–/–.Yaa mice. Flow cytometric analysis showed that the frequency of peripheral Gr-1 but not Gr-1+ monocyte was increased in B6.FcRIIb–/–.Yaa and C/EBPαCre.Yaa but not CD19Cre.Yaa mice, suggesting a link between FcRIIb deficiency on myeloid cells and the high frequency of Gr-1 monocytes. RNA sequencing revealed that compared with Gr-1+ monocytes, Gr-1 monocytes expressed higher levels of the B cell–stimulating cytokines BSF-3, IL-10, and IL-1β, the DC markers CD11c, CD83, and Adamdec1, and the antiapoptotic factors Bcl2 and Bcl6. In conclusion, in Yaa-associated lupus nephritis, FcRIIb on B cells and myeloid cells modulates B cell activation via different but synergistic pathways. Gr-1 monocytes are the most likely candidate myeloid cells involved.



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