Single-cell mass cytometry reveals complex myeloid cell composition in active lesions of progressive multiple sclerosis
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(2020) 8:136
RESEARCH
Open Access
Single-cell mass cytometry reveals complex myeloid cell composition in active lesions of progressive multiple sclerosis Chotima Böttcher1*† , Marlijn van der Poel2†, Camila Fernández-Zapata1†, Stephan Schlickeiser3, Julia K. H. Leman1, Cheng-Chih Hsiao2,4, Mark R. Mizee2, Adelia5, Maria C. J. Vincenten2, Desiree Kunkel6, Inge Huitinga2,7†, Jörg Hamann2,4† and Josef Priller1,8,9*†
Abstract Myeloid cells contribute to inflammation and demyelination in the early stages of multiple sclerosis (MS), but it is still unclear to what extent these cells are involved in active lesion formation in progressive MS (PMS). Here, we have harnessed the power of single-cell mass cytometry (CyTOF) to compare myeloid cell phenotypes in active lesions of PMS donors with those in normal-appearing white matter from the same donors and control white matter from non-MS donors. CyTOF measurements of a total of 74 targeted proteins revealed a decreased abundance of homeostatic and TNFhi microglia, and an increase in highly phagocytic and activated microglia states in active lesions of PMS donors. Interestingly, in contrast to results obtained from studies of the inflammatory early disease stages of MS, infiltrating monocyte-derived macrophages were scarce in active lesions of PMS, suggesting fundamental differences of myeloid cell composition in advanced stages of PMS. Keywords: Progressive multiple sclerosis, Mass cytometry, Microglia, Myeloid cells, Active lesion
Introduction Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) which leads to demyelinating lesions and diffuse neurodegeneration spreading throughout the white and grey matter of the brain and the spinal cord [1, 2]. In most cases (85–90% of patients with MS), the disease starts with a relapsing-remitting course (RRMS), which may develop into a progressive course (secondary progressive MS, SPMS) with ongoing neuroinflammation [3, 4]. For some MS patients (10–15% of patients), neurological disability increases progressively over time without relapse or remission (primary progressive MS, PPMS). From a * Correspondence: [email protected]; [email protected] † Chotima Böttcher, Marlijn van der Poel, Camila Fernández-Zapata, Inge Huitinga, Jörg Hamann and Josef Priller contributed equally to this work. 1 Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité – Universitätsmedizin Berlin, Berlin, Germany Full list of author information is available at the end of the article
neuropathological perspective, MS lesions are characterized as active, mixed active/inactive, inactive remyelinated (shadow plaques), or inactive lesions, based on demyelination and the presence of HLA-DR+ myeloid cells [1, 5]. Both active and mixed active/inactive lesions are characterized by the loss of myelin and the presence of activated foamy microglia/macrophages containing myelin, indicating that microglia/macrophages play a pathogenic role in MS [1, 5]. Active lesions are thought to be th
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