%0 Journal Article
%A Friedrich, Mirco
%A Kehl, Niklas
%A Engelke, Niko
%A Kraus, Josephine
%A Lindner, Katharina
%A Münch, Philipp
%A Mildenberger, Iris
%A Groden, Christoph
%A Gass, Achim
%A Etminan, Nima
%A Fatar, Marc
%A von Deimling, Andreas
%A Reuss, David
%A Platten, Michael
%A Bunse, Lukas
%T Intrathecal activation of CD8+ memory T cells in IgG4-related disease of the brain parenchyma.
%J EMBO molecular medicine
%V 13
%N 8
%@ 1757-4684
%C Heidelberg
%I EMBO Press
%M DKFZ-2021-01569
%P e13953
%D 2021
%Z #EA:D170#LA:D170# / 2021 Aug 9;13(8):e13953 / HI-TRON
%X IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder signified by aberrant infiltration of IgG4-restricted plasma cells into a variety of organs. Clinical presentation is heterogeneous, and pathophysiological mechanisms of IgG4-RD remain elusive. There are very few cases of IgG4-RD with isolated central nervous system manifestation. By leveraging single-cell sequencing of the cerebrospinal fluid (CSF) of a patient with an inflammatory intracranial pseudotumor, we provide novel insights into the immunopathophysiology of IgG4-RD. Our data illustrate an IgG4-RD-associated polyclonal T-cell response in the CSF and an oligoclonal T-cell response in the parenchymal lesions, the latter being the result of a multifaceted cell-cell interaction between immune cell subsets and pathogenic B cells. We demonstrate that CD8+ T effector memory cells might drive and sustain autoimmunity via macrophage migration inhibitory factor (MIF)-CD74 signaling to immature B cells and CC-chemokine ligand 5 (CCL5)-mediated recruitment of cytotoxic CD4+ T cells. These findings highlight the central role of T cells in sustaining IgG4-RD and open novel avenues for targeted therapies.
%K CSF single-cell sequencing (Other)
%K IgG4-related disease (Other)
%K cytotoxic T helper cell (Other)
%K inflammatory pseudotumor (Other)
%K pathogenic B-cell (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34254741
%R 10.15252/emmm.202113953
%U https://inrepo02.dkfz.de/record/169822