Retinoic acid-induced IgG production in TLR-activated human primary B cells involves ULK1-mediated autophagy

Autophagy
Agnete Bratsberg EriksenHeidi Kiil Blomhoff

Abstract

In the present study we have established a vital role of autophagy in retinoic acid (RA)-induced differentiation of toll-like receptor (TLR)-stimulated human B cells into Ig-secreting cells. Thus, RA enhanced autophagy in TLR9- and CD180-stimulated peripheral blood B cells, as revealed by increased levels of the autophagosomal marker LC3B-II, enhanced colocalization between LC3B and the lysosomal marker Lyso-ID, by a larger percentage of cells with more than 5 characteristic LC3B puncta, and by the concomitant reduction in the level of SQSTM1/p62. Furthermore, RA induced expression of the autophagy-inducing protein ULK1 at the transcriptional level, in a process that required the retinoic acid receptor RAR. By inhibiting autophagy with specific inhibitors or by knocking down ULK1 by siRNA, the RA-stimulated IgG production in TLR9- and CD180-mediated cells was markedly reduced. We propose that the identified prominent role of autophagy in RA-mediated IgG-production in normal human B cells provides a novel mechanism whereby vitamin A exerts its important functions in the immune system.

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Citations

Mar 1, 2016·Frontiers in Immunology·Masashi Kanayama, Mari L Shinohara
Oct 6, 2017·Cell Death & Disease·Lixian YangHongchuan Jin
Mar 20, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karin Margaretha GilljamHeidi Kiil Blomhoff
Sep 2, 2020·Cells·Prashanta SilwalEun-Kyeong Jo
Aug 16, 2018·Frontiers in Immunology·Heng YinQianjin Lu

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Methods Mentioned

BETA
confocal microscopy
PCR
ELISA

Software Mentioned

GeneTools
Image Stream analysis
GeneSnap
PASW Statistics
MatInspector
Image Stream
Matrix
IDEAS

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