Deciphering immune mechanisms in chronic inflammatory demyelinating polyneuropathies
Jolien Wolbert, Mandy I. Cheng, Gerd Meyer zu Horste, Maureen A. Su
Jolien Wolbert, Mandy I. Cheng, Gerd Meyer zu Horste, Maureen A. Su
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Review

Deciphering immune mechanisms in chronic inflammatory demyelinating polyneuropathies

Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease of the peripheral nerves that presents with either chronic progression or relapsing disease. Recent studies in samples from patients with CIDP and mouse models have delineated how defects in central (thymic) and peripheral (extrathymic) immune tolerance mechanisms can cause PNS autoimmunity. Notably, nerve parenchymal cells actively contribute to local autoimmunity and also control disease outcome. Here, we outline how emerging technologies increasingly enable an integrated view of how immune cells and PNS parenchymal cells communicate in CIDP. We also relate the known heterogeneity of clinical presentation with specific underlying mechanisms. For example, a severe subtype of CIDP with tremor is associated with pathogenic IgG4 autoantibodies against nodal and paranodal proteins. An improved understanding of pathogenic mechanisms in CIDP will form the basis for more effective mechanism-based therapies.

Authors

Jolien Wolbert, Mandy I. Cheng, Gerd Meyer zu Horste, Maureen A. Su

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Figure 2

Overview of recently developed RNA-seq techniques.

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Overview of recently developed RNA-seq techniques. (A) Whole genome bulk...
(A) Whole genome bulk RNA-seq involves the digestion of tissue and analysis of all transcripts pooled together. This analysis is only tissue or cell specific when performed on presorted, fluorescently labeled cells. (B) scRNA-seq combined with (multiplex) RNA in situ hybridization. scRNA-seq still involves tissue digestion, but transcriptome analysis reaches a single-cell level. Microfluidics techniques are used to bring cells together with oligo-labeled beads and lysis buffer in droplets to allow the identification of all single cells after sequencing at the bulk level. Spatial information from marker genes can be acquired by multiplexed RNA in situ hybridization techniques of known RNA probes or computational comparison with known gene expression atlases. (C) Whole tissue sections are permeabilized on top of glass slides bound with oligonucleotides encoding spatial information. Barcoded transcriptomes are processed for genome-wide RNA-seq. With an optimized resolution of 2 μm, this new technique makes it possible to detect the single-cell transcriptome without losing the tissue spatial orientation. Illustrated by Rachel Davidowitz.