Truncation of CXCL12 by CD26 reduces its CXC chemokine receptor 4- and atypical chemokine receptor 3-dependent activity on endothelial cells and lymphocytes

Different contributions of chemokine N‐terminal features attest to a different ligand binding mode and a bias towards activation of ACKR3/CXCR7 compared with CXCR4 and CXCR3

“…Although CXCL11 3–73 showed ~5‐fold reduction in binding to ACKR3 compared to CXCL11 WT , the deletion of the first two residues of CXCL11 decreased binding to CXCR3 to a larger extent (~40 fold) and, more importantly, had only a modest effect on ACKR3 activation (Proost et al, , ). Our results are in agreement with data from a recent study on proteolyzed CXCL12 and its interactions with CXCR4 and ACKR3 (Janssens et al, ).…”

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

“…Although DPP4 is responsible for proteolytic cleavage of a wide range of substrates, most of DPP4-related researches have been focused on the incretin hormones GLP-1 or GIP for T2DM treatment (Ahren & Hughes, 2005;Baggio & Drucker, 2007;Unniappan et al, 2006). In addition to incretins, cytokines (Broxmeyer et al, 2012;O'Leary et al, 2017;Wesley, McGroarty, & Homoyouni, 2005), chemokines (Barreira da Silva et al, 2015;De La Luz Sierra et al, 2004;Hollande et al, 2019;Janssens et al, 2017;Oravecz et al, 1997;Proost et al, 1999;Proost et al, 2001;Qin et al, 2018), and some neuropeptides (Frerker et al, 2007;Guieu et al, 2006) have been identified as its substrates (Table 2), thereby, allowing DPP4 to regulate immune responses.…”

“…CXCL12/SDF-1 acts through the G protein-coupled CXCR4. Proteolytic cleavage of CXCL12 by DPP4 generates CXCL12(3-68) and results in a reduced CXCR4 affinity and a loss of its calcium-dependent signaling and chemotactic properties (De La Luz Sierra et al, 2004;Janssens et al, 2017).…”

The emerging role of dipeptidyl-peptidase-4 as a therapeutic target in lung disease

“…DPP-4 has intrinsic ectopeptidase activity and modulates chemokines, which can mobilize cancer cells. Tumor immune surveillance may be also influenced by DPP-4, given that it has catalytic activity, with respect to both CXCL10 and CXCL12 that would otherwise assist in lymphocyte migration [51,52]. Moreover, DPP-4 is known to bind matrix metalloproteinases (MMPs), which are proteinases that permit cell migration by removing abundant structural proteins such as collagens, laminins, and proteoglycans, thereby allowing the mobilization of cancer cells through solid tissues [53].…”