Macrophage CD40 signaling drives experimental autoimmune encephalomyelitis.

ABSTRACT: The costimulatory CD40L-CD40 dyad plays a major role in multiple sclerosis (MS). CD40 is highly expressed on MHCII⁺ B cells, dendritic cells and macrophages in human MS lesions. Here we investigated the role of the CD40 downstream signaling intermediates TNF receptor-associated factor 2 (TRAF2) and TRAF6 in MHCII⁺ cells in experimental autoimmune encephalomyelitis (EAE). Both MHCII-CD40-Traf2^-/- and MHCII-CD40-Traf6^-/- mice showed a reduction in clinical signs of EAE and prevented demyelination. However, only MHCII-CD40-Traf6^-/- mice displayed a decrease in myeloid and lymphoid cell infiltration into the CNS that was accompanied by reduced levels of TNF-α, IL-6 and IFN-γ. As CD40-TRAF6 interactions predominantly occur in macrophages, w

SUBMITTER: Aarts SA 

PROVIDER: S-EPMC6519352 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature