TY  - JOUR
AU  - Friedrich, Mirco
AU  - Kehl, Niklas
AU  - Engelke, Niko
AU  - Kraus, Josephine
AU  - Lindner, Katharina
AU  - Münch, Philipp
AU  - Mildenberger, Iris
AU  - Groden, Christoph
AU  - Gass, Achim
AU  - Etminan, Nima
AU  - Fatar, Marc
AU  - von Deimling, Andreas
AU  - Reuss, David
AU  - Platten, Michael
AU  - Bunse, Lukas
TI  - Intrathecal activation of CD8+ memory T cells in IgG4-related disease of the brain parenchyma.
JO  - EMBO molecular medicine
VL  - 13
IS  - 8
SN  - 1757-4684
CY  - Heidelberg
PB  - EMBO Press
M1  - DKFZ-2021-01569
SP  - e13953
PY  - 2021
N1  - #EA:D170#LA:D170# / 2021 Aug 9;13(8):e13953 / HI-TRON
AB  - 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.
KW  - CSF single-cell sequencing (Other)
KW  - IgG4-related disease (Other)
KW  - cytotoxic T helper cell (Other)
KW  - inflammatory pseudotumor (Other)
KW  - pathogenic B-cell (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34254741
DO  - DOI:10.15252/emmm.202113953
UR  - https://inrepo02.dkfz.de/record/169822
ER  -