Circulating Senescent Myeloid Cells Infiltrate the Brain and Cause Neurodegeneration in Histiocytic Disorders

Authors

C Matthias Wilk
Flurin Cathomas
Orsolya Török
Jessica Le Berichel
Matthew D Park
Camille Bigenwald
George R Heaton
Pauline Hamon
Leanna Troncoso
Brooks P Scull
Diana Dangoor
Aymeric Silvin
Ryan Fleischmann
Meriem Belabed
Howard Lin
Elias Merad Taouli
Steffen Boettcher
Long Li
Antonio Aubry
Markus G Manz
Julia K Kofler
Zhenyu Yue
Sergio A Lira
Florent Ginhoux
John F Crary
Kenneth L McClain
Jennifer L Picarsic
Scott J Russo
Carl E Allen
Miriam Merad

Language

English

Publication Date

12-12-2023

Journal

Immunity

DOI

10.1016/j.immuni.2023.11.011

PMID

38091952

PMCID

PMC11587932

PubMedCentral® Posted Date

12-12-2024

PubMedCentral® Full Text Version

Author MSS

Abstract

Neurodegenerative diseases (ND) are characterized by progressive loss of neuronal function. Mechanisms of ND pathogenesis are incompletely understood, hampering the development of effective therapies. Langerhans cell histiocytosis (LCH) is an inflammatory neoplastic disorder caused by hematopoietic progenitors expressing mitogen-activated protein kinase (MAPK)-activating mutations that differentiate into senescent myeloid cells that drive lesion formation. Some individuals with LCH subsequently develop progressive and incurable neurodegeneration (LCH-ND). Here, we showed that LCH-ND was caused by myeloid cells that were clonal with peripheral LCH cells. Circulating BRAFV600E

Keywords

Humans, Proto-Oncogene Proteins B-raf, Histiocytosis, Langerhans-Cell, Brain, Myeloid Cells, Cell Differentiation

Published Open-Access

yes

Recommended Citation

Wilk, C Matthias; Cathomas, Flurin; Török, Orsolya; et al., "Circulating Senescent Myeloid Cells Infiltrate the Brain and Cause Neurodegeneration in Histiocytic Disorders" (2023). Faculty, Staff and Students Publications. 6416.
https://digitalcommons.library.tmc.edu/baylor_docs/6416