B cell treatment promotes a neuroprotective microenvironment after traumatic brain injury through reciprocal immunomodulation with infiltrating peripheral myeloid cells.

Publisher: BioMed Central Country of Publication: England NLM ID: 101222974 Publication Model: Electronic Cited Medium: Internet ISSN: 1742-2094 (Electronic) Linking ISSN: 17422094 NLM ISO Abbreviation: J Neuroinflammation Subsets: MEDLINE

Original Publication: [London] : BioMed Central, c2004-

Brain Injuries, Traumatic*/metabolism ; Neuroprotective Agents*/pharmacology; Mice ; Animals ; Interleukin-10/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Neuroprotection ; Interleukin-6/metabolism ; Myeloid Cells/metabolism ; Immunomodulation ; Transforming Growth Factor beta/metabolism ; B-Lymphocytes/metabolism ; Mice, Inbred C57BL ; Microglia/metabolism

Traumatic brain injury (TBI) remains a major cause of death and severe disability worldwide. We found previously that treatment with exogenous naïve B cells was associated with structural and functional neuroprotection after TBI. Here, we used a mouse model of unilateral controlled cortical contusion TBI to investigate cellular mechanisms of immunomodulation associated with intraparenchymal delivery of mature naïve B lymphocytes at the time of injury. Exogenous B cells showed a complex time-dependent response in the injury microenvironment, including significantly increased expression of IL-10, IL-35, and TGFβ, but also IL-2, IL-6, and TNFα. After 10 days in situ, B cell subsets expressing IL-10 or TGFβ dominated. Immune infiltration into the injury predominantly comprised myeloid cells, and B cell treatment did not alter overall numbers of infiltrating cells. In the presence of B cells, significantly more infiltrating myeloid cells produced IL-10, TGFβ, and IL-35, and fewer produced TNFα, interferon-γ and IL-6 as compared to controls, up to 2 months post-TBI. B cell treatment significantly increased the proportion of CD206 ⁺ infiltrating monocytes/macrophages and reduced the relative proportion of activated microglia starting at 4 days and up to 2 months post-injury. Ablation of peripheral monocytes with clodronate liposomes showed that infiltrating peripheral monocytes/macrophages are required for inducing the regulatory phenotype in exogenous B cells. Reciprocally, B cells specifically reduced the expression of inflammatory cytokines in infiltrating Ly6C ⁺ monocytes/macrophages. These data support the hypothesis that peripheral myeloid cells, particularly infiltrating monocyte/macrophages, are key mediators of the neuroprotective immunomodulatory effects observed after B cell treatment.
(© 2023. The Author(s).)

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R01 NS117598 United States NS NINDS NIH HHS; R01NS117598 United States NS NINDS NIH HHS

Keywords: B cells; Immunomodulation; Macrophages; Microglia; Monocytes; Myeloid cells; Traumatic brain injury

130068-27-8 (Interleukin-10)
0 (Tumor Necrosis Factor-alpha)
0 (Interleukin-6)
0 (Neuroprotective Agents)
0 (Transforming Growth Factor beta)

Date Created: 20230531 Date Completed: 20230602 Latest Revision: 20231228

20231228

PMC10230748

10.1186/s12974-023-02812-y

37259118