T cell responses at diagnosis of amyotrophic lateral sclerosis predict disease progression
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, involving neuroinflammation and T cell infiltration in the central nervous system. However, the contribution of T cell responses to the pathology of the disease is not fully understood. Here we show, by flow cytometric analysi...
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Published in | Nature communications Vol. 13; no. 1; pp. 6733 - 13 |
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Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
08.11.2022
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, involving neuroinflammation and T cell infiltration in the central nervous system. However, the contribution of T cell responses to the pathology of the disease is not fully understood. Here we show, by flow cytometric analysis of blood and cerebrospinal fluid (CSF) samples of a cohort of 89 newly diagnosed ALS patients in Stockholm, Sweden, that T cell phenotypes at the time of diagnosis are good predictors of disease outcome. High frequency of CD4
+
FOXP3
−
effector T cells in blood and CSF is associated with poor survival, whereas high frequency of activated regulatory T (Treg) cells and high ratio between activated and resting Treg cells in blood are associated with better survival. Besides survival, phenotypic profiling of T cells could also predict disease progression rate. Single cell transcriptomics analysis of CSF samples shows clonally expanded CD4
+
and CD8
+
T cells in CSF, with characteristic gene expression patterns. In summary, T cell responses associate with and likely contribute to disease progression in ALS, supporting modulation of adaptive immunity as a viable therapeutic option.
Amyotrophic lateral sclerosis (ALS) is a primary neurodegenerative disease, which is characterized by increased immune cell infiltration of the central nervous system. Here authors show that the phenotypic profile of T cells in the blood and cerebrospinal fluid of newly diagnosed ALS patients can predict disease progression, thus providing evidence that T cells contribute to disease pathology. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-022-34526-9 |