Identification of CD23 as a functional receptor for the proinflammatory cytokine AIMP1/p43

Abstract

SummaryAminoacyl-tRNA-synthetase-interacting multifunctional protein 1 (AIMP1/p43) can be secreted to trigger proinflammatory molecules while it is predominantly bound to a cytoplasmic macromolecular protein complex that contains several different aminoacyl-tRNA synthetases. Although its activities as a secreted signaling factor have been well characterized, the functional receptor for its proinflammatory activity has not yet identified. In this study, we have identified the receptor molecule for AIMP1 that mediates the secretion of TNF-a from THP-1 monocytic cells and primary human peripheral blood mononuclear cells (PBMCs). In a screen of 499 soluble receptors we identified CD23, a known low-affinity receptor for IgE, as a high affinity binding partner of AIMP1. We found that downregulation of CD23 attenuated AIMP1-induced TNF-a secretion and AIMP1 binding to THP-1 and PBMCs. We also observed that in THP-1 and PBMCs, AIMP1-induced TNF-a secretion, mediated by CD23, involved activation of ERK1/2. Interestingly, endothelial monocyte activating polypeptide II (EMAP II), the Cterminal fragment of AIMP1 that is also known to work as a proinflammatory cytokine, was incapable of binding to CD23 and of activating ERK1/2. Therefore, identification of CD23 not only explains the inflammatory function of AIMP1 but also provides the first evidence by which the mode of action of AIMP1 can be distinguished from that of its C-terminal domain, EMAP II.

The antibody atliximab attenuates collagen-induced arthritis by neutralizing AIMP1, an inflammatory cytokine that enhances osteoclastogenesis

“…3E). This result suggests that the association of 15B3AF IgG with P2 region of AIMP1 is critical for blocking AIMP1-mediated TNFa secretion, in agreement with finding that the region between aa 101-192 in AIMP1 is critical for TNFa production [28]. Because AIMP1 induces the secretion of inflammatory cytokines via the activation of ERK and NFkB [19], we examined whether 15B3AF IgG could inhibit the AIMP1-mediated activation of ERK and NFkB in THP-1 monocytes.…”

“…2A). Recently, CD23, a low affinity receptor for IgE, was isolated as a receptor for AIMP1 that induces the secretion of TNFa from monocytes and peripheral blood mononuclear cells [28]. CD23 regulates immune cell activation, and its expression is increased in RA [29,30].…”

Association of Aminoacyl-tRNA Synthetases with Cancer

“…Recently, CD23, a known receptor for IgE, was identified as a receptor for secreted AIMP1 [136]. This study showed that downregulation of CD23 reduced the activation of ERK1/2 and AIMP1-dependent cytokine secretion in primary human monocytes.…”

Aminoacyl tRNA Synthetase–Interacting Multifunctional Protein 1 Acts as a Novel B Cell–Activating Factor In Vitro and In Vivo

“…Recently CD23, also known as Fcε receptor II, was reported to be a functional receptor of AIMP1 in monocytes (21). Because CD23 is also a marker of mature B cells, we hypothesized that AIMP1 activates B cells via CD23.…”