Cell-type specific regulation of MARCH1 E3 ubiquitin ligase by the anti-inflammatory cytokine IL-10

Abstract

<b><span style="font-size:10pt;font-family:'Arial','sans-serif';">Membrane-associated RING-CH-1 (MARCH1) is <span>an E3 ubiquitin ligase which targets MHC-II, CD86 </span>and various other molecules for degradation. It is one of the most efficient post-translational regulators of antigen presentation. MARCH1 is expressed in resting immature dendritic cells and B cells but can be induced in other cell types. While activation of most immune cells results in a reduction in MARCH1 gene expression, its anti-inflammatory properties are highlighted by its induction in response to IL-10. Here, we review what is known about the regulation of MARCH1 gene expression in response to IL-10 by various immune cells. We speculate on the role of MARCH1 ininfection, its differential expression pattern and the promise that this E3 ubiquitin ligase holds to influence immune responses and mitigate immune pathologies.</span></b&gt

Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8

“…Toll-like receptor (TLR) ligands trigger an activation program in DCs, known as DC maturation, that includes up-regulation of MHC II and CD86 expression on the plasma membrane, among other receptors ( Wilson et al., 2004 ). Activation also leads to down-regulation of Marchf1 transcription which, combined with fast turn-over of MARCH1, results in negligible expression of the protein in activated DCs ( Young et al., 2008 ; Vega-Ramos et al., 2014 ; De Gassart et al., 2008 ; Galbas and Thibodeau, 2012 ). It has been assumed that this change is responsible for the accumulation of MHC II and CD86 on the plasma membrane during cDC activation, but this has not been directly examined.…”

Physiological Substrates and Ontogeny-Specific Expression of the Ubiquitin Ligases MARCH1 and MARCH8

“…Toll-like receptor (TLR) ligands trigger an activation program in DC, known as DC maturation, that includes upregulation of MHC II and CD86 expression on the plasma membrane, among other receptors [48]. Activation also leads to down-regulation of Marchf1 transcription which, combined with fast turn-over of MARCH1, results in negligible expression of the protein in activated DCs [6][49][50] [51]. It has been assumed that this change is responsible for the accumulation of MHC II and CD86 on the plasma membrane during cDC activation, but this has not been directly examined.…”