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No use, distribution or reproduction is permitted which does not comply with these terms. The former escapes X inactivation. Our group predicts specific endolysosomal-dependent immune responses are driven by the protein products of these genes, which form a complex at the endolysosomal surface. Our previous studies have shown that knocking out CXorf21 increases lysosomal pH in female monocytes, and the present study assesses whether the lysosomal pH in 46,XX women, who overexpress CXorf21 in monocytes, B cells, and dendritic cells DCs , differs from 46,XY men.
Interestingly, T cells and NK cells, which both express low levels of CXorf21, showed no differential pH levels between men and women. Conclusion: We have previously shown that subjects with two or more X-chromosomes have increased CXorf21 expression in specific primary immune cells. Moreover, knockdown of CXorf21 increases lysosomal pH in female monocytes.
The present data show that female monocytes, DC, B cells, where CXorf21 is robustly expressed, have lower lysosomal pH compared to the same immune cell populations from males. While either disease can have its onset throughout the entire lifespan, the peak age of onset for SLE is about 30, while that for SS is in older adulthood. The diseases are also related in regards to pathophysiology. For instance, most risk genes identified in genome wide association studies are shared between SLE and SS 3 β 6.
Pertinent to the work presented herein, another aspect of shared pathophysiology involves interferon. There is increased expression of interferon-regulated genes in peripheral blood mononuclear cells from patients with either disease 7 β Evidence from both human disease 11 β 13 and murine models 14 β 17 suggests that signaling through lysosomal, nucleic acid-binding toll-like receptors TLR 7 and 9 is in part responsible for the pathogenicity, including increased interferon activity in these diseases.
