OX40 induces CCL20 expression in the context of antigen stimulation: An expanding role of co-stimulatory molecules in chemotaxis

Abstract

OX40 is an inducible co-stimulatory molecule expressed by activated T cells. It plays an important role in the activation and proliferation of T lymphocytes. Recently, some co-stimulatory molecules have been shown to direct leukocyte trafficking. Chemotaxis is essential for achieving an effective immune response. CCL20 is an important chemoattractant produced by activated T cells. In this study, using DO11.10 mice whose transgenic T cell receptor specifically recognizes ovalbumin, we demonstrate that ovalbumin induces OX40 expression in CD4+ lymphocytes. Further stimulation of OX40 by OX40 activating antibody up-regulates CCL20 production. Both NF-κB dependent and independent signaling pathways are implicated in the induction of CCL20 by OX40. Finally, we primed the DO11.10 splenocytes with or without OX40 activating antibody in the presence of ovalbumin. Intranasal administration of the cell lysates derived from the cells with OX40 stimulation results in more severe leukocyte infiltration in the lung of DO11.10 mice, which is substantially attenuated by CCL20 blocking antibody. Taken together, this study has shown that activation of OX40 induces CCL20 expression in the presence of antigen stimulation. Thus, our results broaden the role of OX40 in chemotaxis, and reveal a novel effect of co-stimulatory molecules in orchestrating both T cell up-regulation and migration.

Interaction between Campylobacter and intestinal epithelial cells leads to a different proinflammatory response in human and porcine host

“…This proinflammatory chemokine plays a crucial role in the host response to bacterial infection, being essential for the directional trafficking of immature dendritic cells to the infection site (Dieu-Nosjean et al, 1999;Johanesen and Dwinell, 2006). In addition, CCL20 is implicated in the formation and function of mucosal lymphoid tissues via chemoattraction of lymphocytes and dendritic cells toward the epithelial cells surrounding these tissues (Zhong et al, 2010). Johanesen and Dwinell (2006) reported a flagellin independent mechanism to induce expression of CCL20 after C. jejuni infection, contrary to what has been reported in Salmonella spp.…”

Defining the Signature of VISTA on Myeloid Cell Chemokine Responsiveness

“…PD-1 was recently demonstrated to regulate T follicular helper cell positioning and recruitment to the follicle by suppressing CXCR5 signaling and restricting CXCR3 upregulation (54). OX40 has been shown to induce CCL20 expression upon T cell activation by cognate antigen (55) as well as to play a role in the migration of high-affinity CD4 + T cells to B cell follicles (56). To our knowledge, this is the first report of a negative checkpoint regulator that is central to myeloid cell motility and migration.…”

GITR promoter polymorphism contributes to risk of coal workers’ pneumoconiosis: A case–control study from China

“…In previous studies, OX40 signaling was reported to promote the development of rheumatoid arthritis by enhancing expression of Th2 cytokines in the synovial fluid [43,44]. Zhong et al [45] observed that OX40 signaling up-regulated CCL20 production, hence resulting in severe leukocyte infiltration in the lung of DO11.10 mice. In addition, Wilde and coworkers [46] found the expression of OX40 and GITR had a significant correlation with disease activity in patients with Wengener's granulomatosis.…”