Excessive interferon-α signaling in autoimmunity alters glycosphingolipid processing in B cells

Excessive interferon-α signaling in autoimmunity alters glycosphingolipid processing in B cells
Title:
Excessive interferon-α signaling in autoimmunity alters glycosphingolipid processing in B cells
Other Titles:
Journal of Autoimmunity
Publication Date:
27 November 2017
Citation:
Andy Hee-Meng Tan, Arleen Sanny, Sze-Wai Ng, Ying-Swan Ho, Nurhidayah Basri, Alison Ping Lee, Kong-Peng Lam, Excessive interferon-α signaling in autoimmunity alters glycosphingolipid processing in B cells, Journal of Autoimmunity, Volume 89, 2018, Pages 53-62, ISSN 0896-8411, https://doi.org/10.1016/j.jaut.2017.11.004.
Abstract:
Excessive interferon-α (IFN-α) production by innate immune cells is a hallmark of autoimmune diseases. What other cell type secretes IFN-α and how IFN-α affects immune cell metabolism and homeostasis in autoimmunity are largely unclear. Here, we report that autoimmune B cells, arising from two different B cell-specific genetic lesions in mice, secrete IFN-α. In addition, IFN-α, found in abundance in autoimmunity, elicited profound changes in the B cell lipidome, increasing their expression of glycosphingolipids (GSLs) and leading to their CD1d-mediated depletion of iNKT cells in vitro and in vivo. IFN-α receptor blockade could reverse the loss of iNKT cells. Excessive stimulation of B cells with IFN-α altered the expression of enzymes that catalyze critical steps in GSL processing, increasing the expressions of glucosylceramide synthase (GCS) and globotrihexosylceramide synthase (Gb3S) but decreasing that of α-galactosidase A (α-galA). Inhibiting GCS or restoring α-galA expression prevented iNKT depletion by IFN-α-activated B cells. Taken together, our work indicated that excessive IFN-α perturbs GSL metabolism in B cells which in turn adversely affects iNKT homeostasis.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
This research / project is supported by Bioprocessing Technology Institute, A*STAR
Description:
ISSN:
0896-8411
1095-9157
Files uploaded:
File Size Format Action
There are no attached files.