| First Author | Kurosawa M | Year | 2017 |
| Journal | Arthritis Rheumatol | Volume | 69 |
| Issue | 11 | Pages | 2193-2202 |
| PubMed ID | 28804991 | Mgi Jnum | J:272137 |
| Mgi Id | MGI:6282682 | Doi | 10.1002/art.40230 |
| Citation | Kurosawa M, et al. (2017) NF-kappaB2 Controls the Migratory Activity of Memory T Cells by Regulating Expression of CXCR4 in a Mouse Model of Sjogren's Syndrome. Arthritis Rheumatol 69(11):2193-2202 |
| abstractText | OBJECTIVE: Dysregulated chemokine signaling contributes to autoimmune diseases by facilitating aberrant T cell infiltration into target tissues, but the specific chemokines, receptors, and T cell populations remain largely unidentified. The aim of this study was to examine the role of the potent chemokine CXCL12 and its receptor CXCR4 in the T cell autoimmune response, using alymphoplasia (aly)/aly mice, a model of Sjogren's syndrome (SS). METHODS: T cell phenotypes in the salivary gland of aly/aly mice were evaluated using immunologic analysis. An in vitro migration assay was used to assess T cell migratory activity toward several chemokines. Gene expression of chemokine receptors and transforming growth factor beta receptors (TGFbetaRs) was measured by quantitative reverse transcription-polymerase chain reaction. The CXCR4 antagonist AMD3100 was administered to the aly/aly mice in order to evaluate its suppressive effect on autoimmune lesions. RESULTS: Effector memory T (TEM) cells derived from aly/aly mice demonstrated higher in vitro migratory activity toward CXCL12 than did TEM cells from aly/+ mice. CXCL12 expression was specifically up-regulated in the SS target cells of aly/aly mice. TEM cells from RelB(-/-) mice, but not Nfkb1(-/-) mice, also showed high migratory activity toward CXCL12, implicating a role of the nonclassical RelB/NF-kappaB2 pathway in the regulation of TEM cell migration. TEM cells from aly/aly mice also overexpressed TGFbetaR type I (TGFbetaRI) and TGFbetaRII. The CXCR4 antagonist AMD3100 suppressed autoimmune lesions in aly/aly mice by reducing TEM cell infiltration. CONCLUSION: Our results suggest that the RelB/NF-kappaB2 pathway regulates T cell migration to autoimmune targets through TGFbeta/TGFbetaR-dependent regulation of CXCL12/CXCR4 signaling. This suggests that these signaling pathways are potential therapeutic targets for the treatment of autoimmune diseases. |
