Anti-CD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8+ T-cell cytotoxicity after traumatic brain injury

Zhangying Chen; Kacie P. Ford; Mecca B.A.R. Islam; Hanxiao Wan; Hyebin Han; Abhirami Ramakrishnan; Ryan J. Brown; Veronica Villanueva; Yidan Wang; Booker T. Davis; Craig Weiss; Weiguo Cui; David Gate; Steven J. Schwulst

doi:10.1186/s12974-024-03257-7

Anti-CD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8⁺ T-cell cytotoxicity after traumatic brain injury

Zhangying Chen^*, Kacie P. Ford, Mecca B.A.R. Islam, Hanxiao Wan, Hyebin Han, Abhirami Ramakrishnan, Ryan J. Brown, Veronica Villanueva, Yidan Wang, Booker T. Davis, Craig Weiss, Weiguo Cui, David Gate, Steven J. Schwulst

^*Corresponding author for this work

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

Abstract

Patients aged 65 years and older account for an increasing proportion of patients with traumatic brain injury (TBI). Older TBI patients experience increased morbidity and mortality compared to their younger counterparts. Our prior data demonstrated that by blocking α4 integrin, anti-CD49d antibody (aCD49d Ab) abrogates CD8⁺ T-cell infiltration into the injured brain, improves survival, and attenuates neurocognitive deficits. Here, we aimed to uncover how aCD49d Ab treatment alters local cellular responses in the aged mouse brain. Consequently, mice incur age-associated toxic cytokine and chemokine responses long-term post-TBI. aCD49d Ab attenuates this response along with a T helper (Th)1/Th17 immunological shift and remediation of overall CD8⁺ T cell cytotoxicity. Furthermore, aCD49d Ab reduces CD8⁺ T cells exhibiting higher effector status, leading to reduced clonal expansion in aged, but not young, mouse brains with chronic TBI. Together, aCD49d Ab is a promising therapeutic strategy for treating TBI in the older people.

Original language	English (US)
Article number	267
Journal	Journal of neuroinflammation
Volume	21
Issue number	1
DOIs	https://doi.org/10.1186/s12974-024-03257-7
State	Published - Dec 2024

Funding

We thank the Mechanisms of Aging & Dementia Training Program and the Center for Human Immunobiology at Northwestern University for giving scientific advice. We thank University Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, IL, for the use of the Flow Cytometry Core Facility. The Lurie Cancer Center is supported in part by an NCI Cancer Center Support Grant #P30 CA060553., the NUSeq Core. This work was supported by the Northwestern University NUSeq Core Facility. We would also like to acknowledge NIH Grant 1S10OD025120 for the 10x Chromium housed in the NUSeq Facility. Lastly, this work was supported by the Northwestern University Behavioral Phenotyping Core. The work by the authors is supported through the National Institute of Neurological Disorders and Stroke (NINDS), NIH (R01 NS127865), National Institute of Aging (NIA), NIH (T32 AG020506), and Diana Jacobs Kalman/American Federation for Aging Research (AFAR) Scholarships for Research in the Biology of Aging.

ASJC Scopus subject areas

General Neuroscience
Immunology
Neurology
Cellular and Molecular Neuroscience

Access to Document

10.1186/s12974-024-03257-7

Cite this

Chen, Z., Ford, K. P., Islam, M. B. A. R., Wan, H., Han, H., Ramakrishnan, A., Brown, R. J., Villanueva, V., Wang, Y., Davis, B. T., Weiss, C., Cui, W., Gate, D., & Schwulst, S. J. (2024). Anti-CD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8⁺ T-cell cytotoxicity after traumatic brain injury. Journal of neuroinflammation, 21(1), Article 267. https://doi.org/10.1186/s12974-024-03257-7

@article{730c742c0b8d4c53b910356515ef337c,

title = "Anti-CD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8+ T-cell cytotoxicity after traumatic brain injury",

abstract = "Patients aged 65 years and older account for an increasing proportion of patients with traumatic brain injury (TBI). Older TBI patients experience increased morbidity and mortality compared to their younger counterparts. Our prior data demonstrated that by blocking α4 integrin, anti-CD49d antibody (aCD49d Ab) abrogates CD8+ T-cell infiltration into the injured brain, improves survival, and attenuates neurocognitive deficits. Here, we aimed to uncover how aCD49d Ab treatment alters local cellular responses in the aged mouse brain. Consequently, mice incur age-associated toxic cytokine and chemokine responses long-term post-TBI. aCD49d Ab attenuates this response along with a T helper (Th)1/Th17 immunological shift and remediation of overall CD8+ T cell cytotoxicity. Furthermore, aCD49d Ab reduces CD8+ T cells exhibiting higher effector status, leading to reduced clonal expansion in aged, but not young, mouse brains with chronic TBI. Together, aCD49d Ab is a promising therapeutic strategy for treating TBI in the older people.",

author = "Zhangying Chen and Ford, {Kacie P.} and Islam, {Mecca B.A.R.} and Hanxiao Wan and Hyebin Han and Abhirami Ramakrishnan and Brown, {Ryan J.} and Veronica Villanueva and Yidan Wang and Davis, {Booker T.} and Craig Weiss and Weiguo Cui and David Gate and Schwulst, {Steven J.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1186/s12974-024-03257-7",

language = "English (US)",

volume = "21",

journal = "Journal of neuroinflammation",

issn = "1742-2094",

publisher = "BioMed Central",

number = "1",

}

Chen, Z, Ford, KP, Islam, MBAR, Wan, H, Han, H, Ramakrishnan, A, Brown, RJ, Villanueva, V, Wang, Y, Davis, BT, Weiss, C , Cui, W , Gate, D & Schwulst, SJ 2024, 'Anti-CD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8⁺ T-cell cytotoxicity after traumatic brain injury', Journal of neuroinflammation, vol. 21, no. 1, 267. https://doi.org/10.1186/s12974-024-03257-7

TY - JOUR

T1 - Anti-CD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8+ T-cell cytotoxicity after traumatic brain injury

AU - Chen, Zhangying

AU - Ford, Kacie P.

AU - Islam, Mecca B.A.R.

AU - Wan, Hanxiao

AU - Han, Hyebin

AU - Ramakrishnan, Abhirami

AU - Brown, Ryan J.

AU - Villanueva, Veronica

AU - Wang, Yidan

AU - Davis, Booker T.

AU - Weiss, Craig

AU - Cui, Weiguo

AU - Gate, David

AU - Schwulst, Steven J.

PY - 2024/12

Y1 - 2024/12

N2 - Patients aged 65 years and older account for an increasing proportion of patients with traumatic brain injury (TBI). Older TBI patients experience increased morbidity and mortality compared to their younger counterparts. Our prior data demonstrated that by blocking α4 integrin, anti-CD49d antibody (aCD49d Ab) abrogates CD8+ T-cell infiltration into the injured brain, improves survival, and attenuates neurocognitive deficits. Here, we aimed to uncover how aCD49d Ab treatment alters local cellular responses in the aged mouse brain. Consequently, mice incur age-associated toxic cytokine and chemokine responses long-term post-TBI. aCD49d Ab attenuates this response along with a T helper (Th)1/Th17 immunological shift and remediation of overall CD8+ T cell cytotoxicity. Furthermore, aCD49d Ab reduces CD8+ T cells exhibiting higher effector status, leading to reduced clonal expansion in aged, but not young, mouse brains with chronic TBI. Together, aCD49d Ab is a promising therapeutic strategy for treating TBI in the older people.

AB - Patients aged 65 years and older account for an increasing proportion of patients with traumatic brain injury (TBI). Older TBI patients experience increased morbidity and mortality compared to their younger counterparts. Our prior data demonstrated that by blocking α4 integrin, anti-CD49d antibody (aCD49d Ab) abrogates CD8+ T-cell infiltration into the injured brain, improves survival, and attenuates neurocognitive deficits. Here, we aimed to uncover how aCD49d Ab treatment alters local cellular responses in the aged mouse brain. Consequently, mice incur age-associated toxic cytokine and chemokine responses long-term post-TBI. aCD49d Ab attenuates this response along with a T helper (Th)1/Th17 immunological shift and remediation of overall CD8+ T cell cytotoxicity. Furthermore, aCD49d Ab reduces CD8+ T cells exhibiting higher effector status, leading to reduced clonal expansion in aged, but not young, mouse brains with chronic TBI. Together, aCD49d Ab is a promising therapeutic strategy for treating TBI in the older people.

UR - http://www.scopus.com/inward/record.url?scp=85206872230&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85206872230&partnerID=8YFLogxK

U2 - 10.1186/s12974-024-03257-7

DO - 10.1186/s12974-024-03257-7

M3 - Article

C2 - 39427160

AN - SCOPUS:85206872230

SN - 1742-2094

VL - 21

JO - Journal of neuroinflammation

JF - Journal of neuroinflammation

IS - 1

M1 - 267

ER -