TY  - JOUR
A1  - Rovituso, Damiano M.
A1  - Scheffler, Laura
A1  - Wunsch, Marie
A1  - Kleinschnitz, Christoph
A1  - Dörck, Sebastian
A1  - Ulzheimer, Jochen
A1  - Bayas, Antonios
A1  - Steinman, Lawrence
A1  - Ergün, Süleyman
A1  - Kuerten, Stefanie
T1  - CEACAM1 mediates B cell aggregation in central nervous system autoimmunity
JF  - Scientific Reports
N2  - B cell aggregates in the central nervous system (CNS) have been associated with rapid disease progression in patients with multiple sclerosis (MS). Here we demonstrate a key role of carcinoembryogenic antigen-related cell adhesion molecule1 (CEACAM1) in B cell aggregate formation in MS patients and a B cell-dependent mouse model of MS. CEACAM1 expression was increased on peripheral blood B cells and CEACAM1\(^+\) B cells were present in brain infiltrates of MS patients. Administration of the anti-CEACAM1 antibody T84.1 was efficient in blocking aggregation of B cells derived from MS patients. Along these lines, application of the monoclonal anti-CEACAM1 antibody mCC1 was able to inhibit CNS B cell aggregate formation and significantly attenuated established MS-like disease in mice in the absence of any adverse effects. CEACAM1 was co-expressed with the regulator molecule T cell immunoglobulin and mucin domain −3 (TIM-3) on B cells, a novel molecule that has recently been described to induce anergy in T cells. Interestingly, elevated coexpression on B cells coincided with an autoreactive T helper cell phenotype in MS patients. Overall, these data identify CEACAM1 as a clinically highly interesting target in MS pathogenesis and open new therapeutic avenues for the treatment of the disease.
KW  - autoimmunity
KW  - multiple sclerosis
KW  - neuroimmunology
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147690
VL  - 6
ER  - 
TY  - JOUR
A1  - Koeniger, Tobias
A1  - Bell, Luisa
A1  - Mifka, Anika
A1  - Enders, Michael
A1  - Hautmann, Valentin
A1  - Mekala, Subba Rao
A1  - Kirchner, Philipp
A1  - Ekici, Arif B.
A1  - Schulz, Christian
A1  - Wörsdörfer, Philipp
A1  - Mencl, Stine
A1  - Kleinschnitz, Christoph
A1  - Ergün, Süleyman
A1  - Kuerten, Stefanie
T1  - Bone marrow‐derived myeloid progenitors in the leptomeninges of adult mice
JF  - Stem Cells
N2  - Although the bone marrow contains most hematopoietic activity during adulthood, hematopoietic stem and progenitor cells can be recovered from various extramedullary sites. Cells with hematopoietic progenitor properties have even been reported in the adult brain under steady‐state conditions, but their nature and localization remain insufficiently defined. Here, we describe a heterogeneous population of myeloid progenitors in the leptomeninges of adult C57BL/6 mice. This cell pool included common myeloid, granulocyte/macrophage, and megakaryocyte/erythrocyte progenitors. Accordingly, it gave rise to all major myelo‐erythroid lineages in clonogenic culture assays. Brain‐associated progenitors persisted after tissue perfusion and were partially inaccessible to intravenous antibodies, suggesting their localization behind continuous blood vessel endothelium such as the blood‐arachnoid barrier. Flt3\(^{Cre}\) lineage tracing and bone marrow transplantation showed that the precursors were derived from adult hematopoietic stem cells and were most likely continuously replaced via cell trafficking. Importantly, their occurrence was tied to the immunologic state of the central nervous system (CNS) and was diminished in the context of neuroinflammation and ischemic stroke. Our findings confirm the presence of myeloid progenitors at the meningeal border of the brain and lay the foundation to unravel their possible functions in CNS surveillance and local immune cell production.
KW  - hematopoietic
KW  - meninges
KW  - mouse
KW  - myeloid
KW  - progenitor
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224452
VL  - 39
IS  - 2
SP  - 227
EP  - 239
ER  -