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RNA sequencing of CD45-negative cells isolated from CNS and lung of GM-CSFind x CD4-CreERT2 and control mice

ABSTRACT: Elevated frequencies of GM-CSF-producing helper T (TH) cells are consistently found in multiple sclerosis (MS) patients and GM-CSF expression is a non-redundant feature of pathogenic TH cells in preclinical models of MS. GM-CSF activates an inflammatory signature in monocytes, and their progeny are the most abundant cellular infiltrate in acute MS lesions. To model deregulated GM-CSF levels, we generated a transgenic mouse line allowing the induction of GM-CSF expression in mature, peripheral TH cells. This antigen-independent GM-CSF release induced severe neurological deficits with almost 100% penetrance, accompanied by the infiltration of inflammatory monocyte-derived myeloid cells into the brain stem and spinal cord. Other organs did not show obvious signs for clinical pathology, despite also being infiltrated by inflammatory myeloid cells. We aim to unravel differences between organs, their responses by sequencing CD45-negative tissue cells isolate from the CNS and the lung.

INSTRUMENT(S): BD FACS Aria III, Illumina HiSeq 2500

ORGANISM(S): Mus musculus

SUBMITTER: Sabine Spath

PROVIDER: E-MTAB-5414 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Differential analysis of GM-CSF-induced inflammatory monocyte-derived cells (MCs) isolated from various organs

Project description:Elevated frequencies of GM-CSF-producing helper T (TH) cells are consistently found in multiple sclerosis (MS) patients and GM-CSF expression is a non-redundant feature of pathogenic TH cells in preclinical models of MS. GM-CSF activates an inflammatory signature in monocytes, and their progeny are the most abundant cellular infiltrate in acute MS lesions. To model deregulated GM-CSF levels, we generated a transgenic mouse line allowing the induction of GM-CSF expression in mature, peripheral TH cells. This antigen-independent GM-CSF release induced severe neurological deficits with almost 100% penetrance, accompanied by the infiltration of inflammatory monocyte-derived myeloid cells into the brain stem and spinal cord. Other organs did not show obvious signs for clinical pathology, despite also being infiltrated by inflammatory myeloid cells. We aim to unravel differences between organs, their responses and also the potential of tissue destruction by infiltrating cells by sequencing inflammatory myeloid cells isolate from the individual organs.

2017-02-21 | E-MTAB-5412 | biostudies-arrayexpress

NK cell-derived GM-CSF is critical for enhancing pathological arthritis

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