Reduced 2,4‐dinitro‐1‐fluorobenzene‐induced contact hypersensitivity response in IL‐15 receptor α‐deficient mice correlates with diminished CCL5/RANTES and CXCL10/IP‐10 expression

Abstract

Using a model of 2,4-dinitro-1-fluorobenzene-induced contact hypersensitivity (CHS) we found that, as compared with wild-type mice, IL-15 receptor a chain (IL-15Ra)-deficient mice showed significantly less ear swelling. This decreased response was associated with diminished expression of CCL5/RANTES and CXCL10/IP-10, chemokines critical for effector cell recruitment, in the inflamed tissue. We determined that both the number of CD8 + T cells infiltrating the affected skin and the production of CCL5/RANTES by antigen-stimulated CD8 + T cells were decreased in IL-15Ra -/-mice. The lower levels of CXCL10/IP-10 suggested that the IL-15Ra -/-mice had reduced production of IFN-c, the primary inducer of CXCL10/IP-10, which was in fact the case. However, by contrast with CCL5/RANTES, the diminished levels of IFN-c were likely due to the decreased number of skin-infiltrating CD8 + T cells, since IFN-c production by antigen-stimulated CD8 + T cells was comparable between wild-type and IL-15Ra -/-mice. Our data suggest a positive, pro-inflammatory feedback loop involving CCL5/ RANTES, IFN-c and CXCL10/IP-10 that underlies the CHS reaction and that is disrupted, likely primarily by a defect in CCL5/RANTES production, in mice lacking IL-15Ra, resulting in impaired leukocyte recruitment and inflammation. Moreover, it is particularly noteworthy that the defect in CCL5/RANTES expression in CD8 + T cells is intrinsic to the absence of IL-15Ra, indicating that IL-15Ra is critical for CCL5/ RANTES expression in CD8 + T cells.

Immunosuppressive Effect of Quercetin on Dendritic Cell Activation and Function

“…2,4-Dinitro-1-fluorobenzene (DNFB; Sigma-Aldrich)-induced contact hypersensitivity (CHS) was described previously (32). The abdomen of mice were painted with vehicle (olive oil/acetone = 1/4), DNFB (0.5% w/v), DNFB plus DMSO, or DNFB plus quercetin (50 mg) for sensitization.…”

IL-15 and IL-15Rα gene deletion: Effects on T lymphocyte trafficking and the microglial and neuronal responses to facial nerve axotomy

“…IL-15 is a potent T cell chemoattractant (Wilkinson and Liew, 1995). IL-15 and IL-15Rα can modify the expression of T cell chemoattractants including MCP-1, RANTES, and IP-10, chemokines and their receptors that have been implicated in autoimmune T cell infiltration of the CNS [1,2,8,15].…”

“…IL-15 is a potent T cell chemoattractant (Wilkinson and Liew, 1995). IL-15 and IL-15Rα can modify the expression of T cell chemoattractants including MCP-1, RANTES, and IP-10, chemokines and their receptors that have been implicated in autoimmune T cell infiltration of the CNS [1,2,8,15].T lymphocytes migrate in and out of the brain and other nonlymphoid organs, and can be found in very small numbers in the brain under normal physiological conditions [3,6,7]. Facial nerve axotomy in mice leads to T cell migration across an intact blood-brain-barrier (BBB) where…”

“…It is also possible that the markedly reduced numbers of T cells in the axotomized FMN of both strains of KO mice could be associated with secondary changes in other immune processes affected by these gene deletions. The most likely candidates would be T cell chemokines that are known to be affected by IL-15/IL-15Rα expression, in particular chemoattractants MCP-1, RANTES, and IP-10 and their receptors at the site of injury in the brain [1,2,8,15].…”

IL-15 Can Signal via IL-15Rα, JNK, and NF-κB To Drive RANTES Production by Myeloid Cells

“…IL-15 signaling in vivo, particularly mediated by IL-15Ra, also has been shown to be critical for RANTES production (24). In a murine model of 2,4-dinitro-1-fluorobenzene (DNFB)-induced contact hypersensitivity, DNFBtreated IL-15Ra 2/2 mice displayed a significant reduction in inflammation and local production of RANTES compared with those of DNFB-treated wild-type mice (24).…”