| First Author | Brunn A | Year | 2017 |
| Journal | Am J Pathol | Volume | 187 |
| Issue | 1 | Pages | 42-54 |
| PubMed ID | 27842213 | Mgi Jnum | J:239101 |
| Mgi Id | MGI:5824945 | Doi | 10.1016/j.ajpath.2016.09.009 |
| Citation | Brunn A, et al. (2017) Toll-Like Receptor 2, Toll-Like Receptor 4, Myeloid Differentiation Response Gene 88, and Toll-IL-1 Receptor Domain-Containing Adaptor-Inducing Interferon-gamma (TRIF) Selectively Regulate Susceptibility of P0106-125-Induced Murine Experimental Autoimmune Neuritis. Am J Pathol 187(1):42-54 |
| abstractText | The functional relevance of the innate immune system has not yet been dissected in P0106-125-induced murine experimental autoimmune neuritis. Therefore, the role of Toll-like receptor (TLR) 2, TLR4, myeloid differentiation response gene 88, and Toll-IL-1 receptor domain-containing adaptor-inducing interferon-gamma (TRIF), factors critically involved in the TLR signaling pathway, was studied in experimental autoimmune neuritis. In the absence of TLR2, TLR4, myeloid differentiation response gene 88, or TRIF, the clinical course was significantly attenuated compared to wild-type mice. This could be attributed to impaired NF-kappaB activation, as shown by the absence of nuclear translocation of RelA with a decreased expression of IL-6, IL-12p40, and IL-17A. Remarkably, P0106-125-immunized TLR20/0 mice exhibited a delayed recovery as compared to TLR40/0 mice, which was because of an impaired T helper cell 2 polarization. Immunized TLR20/0 mice were unable to induce OX40 and OX40L by matrix metalloproteinase-2 on splenic dendritic cells. Subsequently, M2 polarization was impaired and macrophages were unable to sufficiently induce T regulatory cells (Tregs). Thus, in the recovery phase, Tregs were significantly increased in TLR40/0 mice as compared to wild-type mice, whereas Tregs in immunized TLR20/0 mice were only slightly increased. Our data highlight the relevance of innate immunity and, especially, the tight interaction between the innate and the adaptive immune system, which should be considered for therapeutic approaches of autoimmune diseases. |
