The CSF in neurosarcoidosis contains consistent clonal expansion of CD8 T cells, but not CD4 T cells

Michael A. Paley; Brandi J. Baker; S. Richard Dunham; Nicole Linskey; Claudia Cantoni; Kenneth Lee; Lynn M. Hassman; Jennifer Laurent; Elisha D.O. Roberson; David B. Clifford; Wayne M. Yokoyama

doi:10.1016/j.jneuroim.2022.577860

The CSF in neurosarcoidosis contains consistent clonal expansion of CD8 T cells, but not CD4 T cells

Michael A. Paley, Brandi J. Baker, S. Richard Dunham, Nicole Linskey, Claudia Cantoni, Kenneth Lee, Lynn M. Hassman, Jennifer Laurent, Elisha D.O. Roberson, David B. Clifford, Wayne M. Yokoyama

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

The tissue-specific drivers of neurosarcoidosis remain poorly defined. To identify cerebrospinal fluid (CSF) specific, antigen-driven T and B cell responses, we performed single-cell RNA sequencing of CSF and blood cells from neurosarcoid participants coupled to T and B cell receptor sequencing. In contrast to pulmonary sarcoidosis, which is driven by CD4 T cells, we found CD8 T cell clonal expansion enriched in the neurosarcoid CSF. These CSF-enriched CD8 T cells were composed of two subsets with differential expression of EBI2, CXCR3, and CXCR4. Lastly, our data suggest that IFNγ signaling may distinguish neurosarcoidosis from other neurological disorders.

Original language	English
Article number	577860
Journal	Journal of Neuroimmunology
Volume	367
DOIs	https://doi.org/10.1016/j.jneuroim.2022.577860
State	Published - Jun 15 2022

Keywords

Interferon
Neurosarcoidosis
Sarcoidosis
Single-cell RNA sequencing
T cells
TCR sequencing

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10.1016/j.jneuroim.2022.577860

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title = "The CSF in neurosarcoidosis contains consistent clonal expansion of CD8 T cells, but not CD4 T cells",

abstract = "The tissue-specific drivers of neurosarcoidosis remain poorly defined. To identify cerebrospinal fluid (CSF) specific, antigen-driven T and B cell responses, we performed single-cell RNA sequencing of CSF and blood cells from neurosarcoid participants coupled to T and B cell receptor sequencing. In contrast to pulmonary sarcoidosis, which is driven by CD4 T cells, we found CD8 T cell clonal expansion enriched in the neurosarcoid CSF. These CSF-enriched CD8 T cells were composed of two subsets with differential expression of EBI2, CXCR3, and CXCR4. Lastly, our data suggest that IFNγ signaling may distinguish neurosarcoidosis from other neurological disorders.",

keywords = "Interferon, Neurosarcoidosis, Sarcoidosis, Single-cell RNA sequencing, T cells, TCR sequencing",

author = "Paley, {Michael A.} and Baker, {Brandi J.} and Dunham, {S. Richard} and Nicole Linskey and Claudia Cantoni and Kenneth Lee and Hassman, {Lynn M.} and Jennifer Laurent and Roberson, {Elisha D.O.} and Clifford, {David B.} and Yokoyama, {Wayne M.}",

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doi = "10.1016/j.jneuroim.2022.577860",

language = "English",

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T1 - The CSF in neurosarcoidosis contains consistent clonal expansion of CD8 T cells, but not CD4 T cells

AU - Paley, Michael A.

AU - Baker, Brandi J.

AU - Dunham, S. Richard

AU - Linskey, Nicole

AU - Cantoni, Claudia

AU - Lee, Kenneth

AU - Hassman, Lynn M.

AU - Laurent, Jennifer

AU - Roberson, Elisha D.O.

AU - Clifford, David B.

AU - Yokoyama, Wayne M.

PY - 2022/6/15

Y1 - 2022/6/15

N2 - The tissue-specific drivers of neurosarcoidosis remain poorly defined. To identify cerebrospinal fluid (CSF) specific, antigen-driven T and B cell responses, we performed single-cell RNA sequencing of CSF and blood cells from neurosarcoid participants coupled to T and B cell receptor sequencing. In contrast to pulmonary sarcoidosis, which is driven by CD4 T cells, we found CD8 T cell clonal expansion enriched in the neurosarcoid CSF. These CSF-enriched CD8 T cells were composed of two subsets with differential expression of EBI2, CXCR3, and CXCR4. Lastly, our data suggest that IFNγ signaling may distinguish neurosarcoidosis from other neurological disorders.

AB - The tissue-specific drivers of neurosarcoidosis remain poorly defined. To identify cerebrospinal fluid (CSF) specific, antigen-driven T and B cell responses, we performed single-cell RNA sequencing of CSF and blood cells from neurosarcoid participants coupled to T and B cell receptor sequencing. In contrast to pulmonary sarcoidosis, which is driven by CD4 T cells, we found CD8 T cell clonal expansion enriched in the neurosarcoid CSF. These CSF-enriched CD8 T cells were composed of two subsets with differential expression of EBI2, CXCR3, and CXCR4. Lastly, our data suggest that IFNγ signaling may distinguish neurosarcoidosis from other neurological disorders.

KW - Interferon

KW - Neurosarcoidosis

KW - Sarcoidosis

KW - Single-cell RNA sequencing

KW - T cells

KW - TCR sequencing

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U2 - 10.1016/j.jneuroim.2022.577860

DO - 10.1016/j.jneuroim.2022.577860

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AN - SCOPUS:85127675958

SN - 0165-5728

VL - 367

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

M1 - 577860

ER -

The CSF in neurosarcoidosis contains consistent clonal expansion of CD8 T cells, but not CD4 T cells

Abstract

Keywords

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