TY - JOUR
T1 - Meningeal lymphoid structures are activated under acute and chronic spinal cord pathologies
AU - Cohen, Merav
AU - Giladi, Amir
AU - Raposo, Catarina
AU - Zada, Mor
AU - Li, Baoguo
AU - Ruckh, Julia
AU - Deczkowska, Aleksandra
AU - Mohar, Boaz
AU - Shechter, Ravid
AU - Lichtenstein, Rachel G.
AU - Amit, Ido
AU - Schwartz, Michal
N1 - Funding Information:
Research in the M Schwartz lab is supported by Advanced European Research Council grants (232835), and by the European Seventh Framework Program HEALTH-2011 (279017); Israel Science Foundation (ISF)-research grant no. 991/16; and ISF-Legacy Heritage Bio-medical Science Partnership-research grant no. 1354/15. The research of I Amit is supported by the Seed Networks for the Human Cell Atlas of the Chan Zuckerberg Initiative and by Merck KGaA, Darmstadt. I Amit is an incumbent of the Eden and Steven Romick Professorial Chair, supported by the Howard Hughes Medical Institute International Scholar Award, the European Research Council Consolidator Grant (no. 724471-HemTree2.0), an melanoma research alliance Established Investigator Award (no. 509044), Deutsche Forschungsgemeinschaft (DFG) (no. SFB/ TRR167), the Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine, the Helen and Martin Kimmel awards for innovative investigation, and the award of the Wolfson Foundation and Family Charitable Trust. The Thompson Family Foundation Alzheimer’s Research Fund and the Adelis Foundation also provided support. RG Lichtenstein is supported by Keren Hayesod, Magbit France.
Funding Information:
Research in the M Schwartz lab is supported by Advanced European Research Council grants (232835), and by the European Seventh Framework Program HEALTH-2011 (279017); Israel Science Foundation (ISF)-research grant no. 991/16; and ISF-Legacy Heritage Bio-medical Science Partnershipresearch grant no. 1354/15. The research of I Amit is supported by the Seed Networks for the Human Cell Atlas of the Chan Zuckerberg Initiative and by Merck KGaA, Darmstadt. I Amit is an incumbent of the Eden and Steven Romick Professorial Chair, supported by the Howard Hughes Medical Institute International Scholar Award, the European Research Council Consolidator Grant (no. 724471-HemTree2.0), an melanoma research alliance Established Investigator Award (no. 509044), Deutsche Forschungsgemeinschaft (DFG) (no. SFB/ TRR167), the Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine, the Helen and Martin Kimmel awards for innovative investigation, and the award of the Wolfson Foundation and Family Charitable Trust. The Thompson Family Foundation Alzheimer's Research Fund and the Adelis Foundation also provided support. RG Lichtenstein is supported by Keren Hayesod, Magbit France.
Publisher Copyright:
© 2020 Cohen et al.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Tertiary lymphoid structures (TLS) are organized aggregates of B and T cells formed ectopically during different stages of life in response to inflammation, infection, or cancer. Here, we describe formation of structures reminiscent of TLS in the spinal cord meninges under several central nervous system (CNS) pathologies. After acute spinal cord injury, B and T lymphocytes locally aggregate within the meninges to form TLS-like structures, and continue to accumulate during the late phase of the response to the injury, with a negative impact on subsequent pathological conditions, such as experimental autoimmune encephalomyelitis. Using a chronic model of spinal cord pathology, the mSOD1 mouse model of amyotrophic lateral sclerosis, we further showed by single-cell RNA-sequencing that a meningeal lymphocyte niche forms, with a unique organization and activation state, including accumulation of pre-B cells in the spinal cord meninges. Such a response was not found in the CNS-draining cervical lymph nodes. The present findings suggest that a special immune response develops in the meninges during various neurological pathologies in the CNS, a possible reflection of its immune privileged nature.
AB - Tertiary lymphoid structures (TLS) are organized aggregates of B and T cells formed ectopically during different stages of life in response to inflammation, infection, or cancer. Here, we describe formation of structures reminiscent of TLS in the spinal cord meninges under several central nervous system (CNS) pathologies. After acute spinal cord injury, B and T lymphocytes locally aggregate within the meninges to form TLS-like structures, and continue to accumulate during the late phase of the response to the injury, with a negative impact on subsequent pathological conditions, such as experimental autoimmune encephalomyelitis. Using a chronic model of spinal cord pathology, the mSOD1 mouse model of amyotrophic lateral sclerosis, we further showed by single-cell RNA-sequencing that a meningeal lymphocyte niche forms, with a unique organization and activation state, including accumulation of pre-B cells in the spinal cord meninges. Such a response was not found in the CNS-draining cervical lymph nodes. The present findings suggest that a special immune response develops in the meninges during various neurological pathologies in the CNS, a possible reflection of its immune privileged nature.
UR - http://www.scopus.com/inward/record.url?scp=85097311459&partnerID=8YFLogxK
U2 - 10.26508/LSA.202000907
DO - 10.26508/LSA.202000907
M3 - Article
AN - SCOPUS:85097311459
SN - 2575-1077
VL - 4
JO - Life Science Alliance
JF - Life Science Alliance
IS - 1
M1 - e202000907
ER -