Tertiary lymphoid structures in the choroid plexus in neuropsychiatric lupus

Ariel D. Stock, Evan Der, Sivan Gelb, Michelle Huang, Karen M. Weidenheim, Ayal Ben-Zvi, Chaim Putterman

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The central nervous system manifestations of systemic lupus erythematosus (SLE) remain poorly understood. Given the well-defined role of autoantibodies in other lupus manifestations, extensive work has gone into the identification of neuropathic autoantibodies. However, attempts to translate these findings to patients with SLE have yielded mixed results. We used the MRL/ MpJ-Faslpr/lpr mouse, a well-established, spontaneous model of SLE, to establish the immune effectors responsible for brain disease. Transcriptomic analysis of the MRL/MpJ-Faslpr/lpr choroid plexus revealed an expression signature driving tertiary lymphoid structure formation, including chemokines related to stromal reorganization and lymphocyte compartmentalization. Additionally, transcriptional profiles indicated various stages of lymphocyte activation and germinal center formation. The extensive choroid plexus infiltrate present in MRL/MpJ-Faslpr/lpr mice with overt neurobehavioral deficits included locally proliferating B and T cells, intercellular interactions between lymphocytes and antigen-presenting cells, as well as evidence for in situ somatic hypermutation and class switch recombination. Furthermore, the choroid plexus was a site for trafficking lymphocytes into the brain. Finally, histological evaluation in human lupus patients with neuropsychiatric manifestations revealed increased leukocyte migration through the choroid plexus. These studies identify a potential new pathway underlying neuropsychiatric lupus and support tertiary lymphoid structure formation in the choroid plexus as a novel mechanism of brain-immune interfacing.

Original languageEnglish (US)
Article number:e124203
JournalJCI Insight
Volume4
Issue number11
DOIs
StatePublished - Jun 6 2019

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Choroid Plexus
Systemic Lupus Erythematosus
Lymphocytes
Autoantibodies
Germinal Center
Brain
Brain Diseases
Antigen-Presenting Cells
Lymphocyte Activation
Chemokines
Cell Communication
Genetic Recombination
Leukocytes
B-Lymphocytes
Central Nervous System
Tertiary Lymphoid Structures
T-Lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Tertiary lymphoid structures in the choroid plexus in neuropsychiatric lupus. / Stock, Ariel D.; Der, Evan; Gelb, Sivan; Huang, Michelle; Weidenheim, Karen M.; Ben-Zvi, Ayal; Putterman, Chaim.

In: JCI Insight, Vol. 4, No. 11, :e124203, 06.06.2019.

Research output: Contribution to journalArticle

Stock, Ariel D. ; Der, Evan ; Gelb, Sivan ; Huang, Michelle ; Weidenheim, Karen M. ; Ben-Zvi, Ayal ; Putterman, Chaim. / Tertiary lymphoid structures in the choroid plexus in neuropsychiatric lupus. In: JCI Insight. 2019 ; Vol. 4, No. 11.
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