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000169822 041__ $$aEnglish
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000169822 1001_ $$0P:(DE-He78)1cab354af0aff62f1b8d569477b4be4c$$aFriedrich, Mirco$$b0$$eFirst author$$udkfz
000169822 245__ $$aIntrathecal activation of CD8+ memory T cells in IgG4-related disease of the brain parenchyma.
000169822 260__ $$aHeidelberg$$bEMBO Press$$c2021
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000169822 520__ $$aIgG4-related disease (IgG4-RD) is a fibroinflammatory disorder signified by aberrant infiltration of IgG4-restricted plasma cells into a variety of organs. Clinical presentation is heterogeneous, and pathophysiological mechanisms of IgG4-RD remain elusive. There are very few cases of IgG4-RD with isolated central nervous system manifestation. By leveraging single-cell sequencing of the cerebrospinal fluid (CSF) of a patient with an inflammatory intracranial pseudotumor, we provide novel insights into the immunopathophysiology of IgG4-RD. Our data illustrate an IgG4-RD-associated polyclonal T-cell response in the CSF and an oligoclonal T-cell response in the parenchymal lesions, the latter being the result of a multifaceted cell-cell interaction between immune cell subsets and pathogenic B cells. We demonstrate that CD8+ T effector memory cells might drive and sustain autoimmunity via macrophage migration inhibitory factor (MIF)-CD74 signaling to immature B cells and CC-chemokine ligand 5 (CCL5)-mediated recruitment of cytotoxic CD4+ T cells. These findings highlight the central role of T cells in sustaining IgG4-RD and open novel avenues for targeted therapies.
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000169822 650_7 $$2Other$$aCSF single-cell sequencing
000169822 650_7 $$2Other$$aIgG4-related disease
000169822 650_7 $$2Other$$acytotoxic T helper cell
000169822 650_7 $$2Other$$ainflammatory pseudotumor
000169822 650_7 $$2Other$$apathogenic B-cell
000169822 7001_ $$0P:(DE-He78)fad274ed48f42202270f60e22b0bcdd1$$aKehl, Niklas$$b1$$udkfz
000169822 7001_ $$aEngelke, Niko$$b2
000169822 7001_ $$aKraus, Josephine$$b3
000169822 7001_ $$0P:(DE-He78)9c599f876c762bc78d289674c15ba4a5$$aLindner, Katharina$$b4$$udkfz
000169822 7001_ $$0P:(DE-He78)66bc424b1c5322674c5f9c9d7131f760$$aMünch, Philipp$$b5$$udkfz
000169822 7001_ $$0P:(DE-He78)7daa75b87e6d6e291016ecb54f60b6b3$$aMildenberger, Iris$$b6$$udkfz
000169822 7001_ $$aGroden, Christoph$$b7
000169822 7001_ $$aGass, Achim$$b8
000169822 7001_ $$aEtminan, Nima$$b9
000169822 7001_ $$aFatar, Marc$$b10
000169822 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b11$$udkfz
000169822 7001_ $$0P:(DE-He78)d5149ffd74f42a2fa87a086d66645aaa$$aReuss, David$$b12$$udkfz
000169822 7001_ $$0P:(DE-He78)5ef8651b0f857b9c640aa5b1498c43b5$$aPlatten, Michael$$b13$$udkfz
000169822 7001_ $$0P:(DE-He78)e579130c57e8c686ed1c2dedfa595985$$aBunse, Lukas$$b14$$eLast author$$udkfz
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