Bcl6 controls meningeal Th17-B cell interaction in murine neuroinflammation.
Animals
B-Lymphocytes
/ immunology
Cell Communication
Cytokines
/ metabolism
Encephalomyelitis, Autoimmune, Experimental
/ metabolism
Female
Germinal Center
/ immunology
Inflammation
/ metabolism
Lymphocyte Activation
Male
Meninges
/ immunology
Mice
Mice, Inbred C57BL
Multiple Sclerosis
/ metabolism
Neuroinflammatory Diseases
/ immunology
Parenchymal Tissue
/ immunology
Proto-Oncogene Proteins c-bcl-6
/ metabolism
Th17 Cells
/ immunology
Bcl6
CNS meninges
Th17
ectopic lymphoid tissue
single-cell RNA-seq
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
07 09 2021
07 09 2021
Historique:
accepted:
27
07
2021
received:
06
08
2021
entrez:
4
9
2021
pubmed:
5
9
2021
medline:
5
1
2022
Statut:
ppublish
Résumé
Ectopic lymphoid tissue containing B cells forms in the meninges at late stages of human multiple sclerosis (MS) and when neuroinflammation is induced by interleukin (IL)-17 producing T helper (Th17) cells in rodents. B cell differentiation and the subsequent release of class-switched immunoglobulins have been speculated to occur in the meninges, but the exact cellular composition and underlying mechanisms of meningeal-dominated inflammation remain unknown. Here, we performed in-depth characterization of meningeal versus parenchymal Th17-induced rodent neuroinflammation. The most pronounced cellular and transcriptional differences between these compartments was the localization of B cells exhibiting a follicular phenotype exclusively to the meninges. Correspondingly, meningeal but not parenchymal Th17 cells acquired a B cell-supporting phenotype and resided in close contact with B cells. This preferential B cell tropism for the meninges and the formation of meningeal ectopic lymphoid tissue was partially dependent on the expression of the transcription factor Bcl6 in Th17 cells that is required in other T cell lineages to induce isotype class switching in B cells. A function of Bcl6 in Th17 cells was only detected in vivo and was reflected by the induction of B cell-supporting cytokines, the appearance of follicular B cells in the meninges, and of immunoglobulin class switching in the cerebrospinal fluid. We thus identify the induction of a B cell-supporting meningeal microenvironment by Bcl6 in Th17 cells as a mechanism controlling compartment specificity in neuroinflammation.
Identifiants
pubmed: 34479995
pii: 2023174118
doi: 10.1073/pnas.2023174118
pmc: PMC8433502
pii:
doi:
Substances chimiques
Bcl6 protein, mouse
0
Cytokines
0
Proto-Oncogene Proteins c-bcl-6
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : R01 NS106289
Pays : United States
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Competing interest statement: A patent application covering the method for reconstructing T cell receptor information from 3′ libraries has been applied with the title “Circulation Method to Sequence Immune Repertoires of Individual Cells” under the filing no. LU101949 by X. L. and G.M.z.H. (date of filing: July 29, 2020).
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