Expression and regulation of Schlafen (SLFN) family members in primary human monocytes, monocyte-derived dendritic cells and T cells

Abstract

Schlafen (SLFN/Slfn) family members have been investigated for their involvement in fundamental cellular processes including growth regulation, differentiation and control of viral replication. However, most research has been focused on the characterization of Slfns within the murine system or in human cell lines. Since little is known about SLFNs in primary human immune cells, we set out to analyze the expression and regulation of the six human SLFN genes in monocytes, monocyte-derived dendritic cells (moDCs) and T cells. Comparison of SLFN gene expression across these three cell types showed high mRNA expression of SLFN11 in monocytes and moDCs and high SLFN5 expression in T cells, indicating functional importance within these cell types. Differentiation of monocytes to moDCs leads to the gradual upregulation of SLFN12L and SLFN13 while SLFN12 levels were decreased by differentiation stimuli. Stimulation of moDCs via human rhinovirus, lipopolysaccharide, or IFN-α lead to strong upregulation of SLFN gene expression, while peptidoglycan poorly stimulated regulation of both SLFNs and the classical interferon-stimulated gene MxA. T cell activation was found to downregulate the expression of SLFN5, SLFN12 and SLFN12L, which was reversible upon addition of exogenous IFN-α. In conclusion, we demonstrate, that SLFN gene upregulation is mainly dependent on autocrine type I interferon signaling in primary human immune cells. Rapid decrease of SLFN expression levels following T cell receptor stimulation indicates a role of SLFNs in the regulation of human T cell quiescence.

SCHLAFEN 5 expression correlates with intestinal metaplasia that progresses to gastric cancer

“…SLFN5 staining was generally higher in the gastric stroma compared to gastric glands (Fig. 4B), as expected based upon known Schlafen gene expression in murine and human hematopoietic cells [4,13]. SLFN5 expression was observed in subjects with atrophic gastritis, intestinal metaplasia, and both intestinal and diffuse subtypes of GC (Fig.…”

“…Previous research of Schlafen genes (including SLFN5) indicates that they are up-regulated in mature CD4 + and CD8 + thymocytes and in peripheral resting T cells; and down-regulated after T-cell stimulation [13,19]. In the SLFN8 (group III) transgenic mouse, elevated T-cell expression partially blocked thymocyte transition to mature T cells; and transgenic T cells exhibited a significant reduction in the proliferative response [19].…”

Schlafen 12 Interaction with SerpinB12 and Deubiquitylases Drives Human Enterocyte Differentiation

“…SLFN12 has previously been reported to alter the phenotype of other cells, including prostatic cancer cells [53] and activated T cells [54, 55], and to inhibit dendritic cell differentiation [11]. Slfn4, also intermediate length, regulates myelopoiesis [56].…”

Schlafen 14 (SLFN14) is a novel antiviral factor involved in the control of viral replication

“…For example, SLFN5, SLFN12L, and SLFN13 expression is highest in T cells, whereas SLFN11 expression was more prominent in monocytes and human monocyte-derived dendritic cells (moDCs) (Puck et al, 2015). Basal levels of SLFN12L and SLFN13 expression were relatively low in monocytes, but were upregulated following differentiation into moDCs.…”