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

Autor: Chen Z; Department of Surgery, Division of Trauma and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. jenniechen2024@u.northwestern.edu.; Driskill Graduate Program in Life Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. jenniechen2024@u.northwestern.edu., Ford KP; Department of Surgery, Division of Trauma and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Islam MBAR; Department of Surgery, Division of Trauma and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Wan H; Driskill Graduate Program in Life Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Han H; Department of Surgery, Division of Trauma and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Driskill Graduate Program in Life Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Ramakrishnan A; Driskill Graduate Program in Life Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Brown RJ; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA., Villanueva V; Department of Surgery, Division of Trauma and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Wang Y; Driskill Graduate Program in Life Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA., Davis BT 4th; Department of Surgery, Division of Trauma and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Weiss C; Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA., Cui W; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA., Gate D; The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Schwulst SJ; Department of Surgery, Division of Trauma and Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2024 Oct 19; Vol. 21 (1), pp. 267. Date of Electronic Publication: 2024 Oct 19.
DOI: 10.1186/s12974-024-03257-7
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje