% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Crowley:302328,
      author       = {T. Crowley and J. Chen and K. S. Rosiewicz and L.
                      Jopp-Saile$^*$ and G. Herold and C. Biese and C. Fischer and
                      J. Kerkering and M. Alisch and F. Paul and V. Siffrin},
      title        = {{M}apping {CD}4+ {T} cell diversity in {CSF} to identify
                      endophenotypes of multiple sclerosis.},
      journal      = {Brain communications},
      volume       = {7},
      number       = {3},
      issn         = {2632-1297},
      address      = {[Oxford]},
      publisher    = {Oxford University Press},
      reportid     = {DKFZ-2025-01323},
      pages        = {fcaf231},
      year         = {2025},
      abstract     = {Multiple sclerosis (MS) is a chronic inflammatory CNS
                      disease with heterogeneous manifestation. Prognostic markers
                      for early classification of MS are currently under
                      investigation. Higher diagnostic resolution of cerebrospinal
                      fluid (CSF) has the potential to contribute significantly to
                      patient stratification, which should be especially important
                      for a subgroup of patients with high risk to convert to a
                      progressive disease course. This study aimed to determine
                      whether spectral flow cytometry of CSF cells could identify
                      pathogenic CD4+ T cell subset in MS. Using a two-step
                      approach, we designed a marker panel informed by publicly
                      available transcriptomic datasets from early human MS and
                      our own single-cell RNA sequencing (scRNA-seq) in acute and
                      chronic experimental autoimmune encephalomyelitis (EAE), a
                      murine MS model. Notably, chronic ('phase') markers such as
                      Il7r and Ramp3 (associated with memory T cells), Itgb1
                      (integrin beta-1) and anti-apoptotic genes like Dnaja1,
                      Hsph1 and Jun/AP-1 were enriched in EAE. These markers
                      reflect pro-survival signalling and tissue-residency
                      characteristics, including CXCR6, CD69 and Bhlhe40, which
                      suggest an adaptation of CD4+ T cells towards persistent
                      neuroinflammatory responses in chronic EAE. This
                      phase-specific marker profile highlights CD4+ T cells as
                      both indicators and contributors to disease progression in
                      EAE. Translating these findings to MS datasets, we found an
                      enrichment of phase-specific markers in CSF cells. Spectral
                      flow cytometry in an independent MS cohort revealed distinct
                      memory and effector T cell subsets, indicating unique CSF
                      signatures in MS. This study underscores the heterogeneity
                      and dynamic changes of CD4+ T cells detectable by spectral
                      flow cytometry, enhancing diagnostic resolution of CSF cells
                      and informing more precise therapeutic strategies for MS.},
      keywords     = {T cell subsets (Other) / cerebrospinal fluid (Other) /
                      chronic neuroinflammation (Other) / experimental
                      neuroinflammation (Other) / multiple sclerosis (Other)},
      cin          = {A010},
      ddc          = {610},
      cid          = {I:(DE-He78)A010-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40574973},
      pmc          = {pmc:PMC12199765},
      doi          = {10.1093/braincomms/fcaf231},
      url          = {https://inrepo02.dkfz.de/record/302328},
}