RA also induces the expression of [alpha]4[beta]7 and
CCR9 in ILCs 1 and 3, which is crucial during antiviral and antibacterial responses in the intestinal mucosa; this effect is not observed in ILC2 since the homing receptors expression of these cells is determined during development in the bone marrow [8].
Traficet-EN (CCX282-B) is a specific
CCR9 antagonist with the potential to offer a new approach for the treatment of inflammatory bowel diseases, including Crohn's disease, the companies said.
Besides its potency to induce Tregs, it is accepted that the subset of [CD103.sup-]expressing DCs is particularly capable of, upon encountering an antigen, migration towards the draining MLN and induction of the priming of naive T cells towards
CCR9 and [alpha]4[beta]7 integrin-expressing T cells, which will subsequently differentiate into gut-homing T cells [60, 65, 66].
We observed that DSS challenge of BALB/c mice triggered upregulation of CCR6 (a chemokine for Th17 cells [7]) mRNA, while CCR4,
CCR9, and MCP-1/CCL2 mRNA were significantly increased in DSS-challenged C57BL/6 mice (Figure 6).
T cells of these lymph nodes in turn showed reduced expression of the retinoic acid receptor (RAR) [alpha] and diminished expression of the gut homing markers
CCR9 and [alpha]4[beta]7 integrin.
An increased expression of the CD11a integrin in naive CD45[RA.sup.+] T cells and overexpression of CCR5 and
CCR9 during AVH-E infection have suggested an enhanced recruitment of these cells from periphery to the target tissue during the early phase of infection.
Moreover, CAV1, CD200R1, HRASLS2, MIA, TNFRSF17, CXCR3, AQP3,
CCR9, IFNAR1, and CEACAM1 among the top twenty upregulated genes as well as EIF1AY, DDX3Y UTY, IL7R, IGFBP7, and GNLY among the top twenty downregulated genes are involved in immune function of organism, while other genes function in immune responses was not clearly identified.
CCR7,
CCR9, CXCR1, and CXCR2 are also detected in tumor cells and their ligands can induce the chemotaxis of the corresponding receptor-expressing cells [78, 79].
CCL25, via
CCR9, confers a survival advantage to breast cancer cells by inhibiting cisplatin-induced apoptosis in a PI3Kdependent manner, in addition to activating cell survival signals through Akt [49].
Moreover, these cells express high levels of CXCR3, CXCR6, and
CCR9, all of which are involved in lymphocyte migration to tissues.