Journal Article

DKFZ-2021-01569

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Intrathecal activation of CD8+ memory T cells in IgG4-related disease of the brain parenchyma.

Friedrich, M. (First author)DKFZ* ; Kehl, N.DKFZ* ; Engelke, N. ; Kraus, J. ; Lindner, K.DKFZ* ; Münch, P.DKFZ* ; Mildenberger, I.DKFZ* ; Groden, C. ; Gass, A. ; Etminan, N. ; Fatar, M. ; von Deimling, A.DKFZ* ; Reuss, D.DKFZ* ; Platten, M.DKFZ* ; Bunse, L. (Last author)DKFZ*

2021
EMBO Press Heidelberg

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Please use a persistent id in citations: doi:10.15252/emmm.202113953

Abstract: 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.

Keyword(s): CSF single-cell sequencing ; IgG4-related disease ; cytotoxic T helper cell ; inflammatory pseudotumor ; pathogenic B-cell

Note: #EA:D170#LA:D170# / 2021 Aug 9;13(8):e13953 / HI-TRON

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Contributing Institute(s):

1. KKE Neuroimmunologie und Hirntumorimmunologie (D170)
2. DKTK HD zentral (HD01)
3. KKE Neuropathologie (B300)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2021

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Database coverage:
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