NHRI researcher reports lipocalin‐2 mediates the rejection of neural transplants

Cell replacement therapy has been investigated as a potential treatment for neurological disorders including stroke, Parkinson’s disease, and traumatic brain injury. Intracerebral transplantation may, however, trigger an immune response that results in rejection of the engrafted neurons. Thus, understanding the immune mechanisms of graft rejection is essential to improve cell replacement therapy for neurological disorders. Dr. Wen-Hai Chou and his team from the Center for Neuropsychiatric Research investigated the potential roles of lipocalin-2 (LCN2) and brain type organic cation transporter (BOCT) in neural transplantation with findings published in The FASEB Journal.

Dr. Chou’s team cultured and differentiated Lund human mesencephalic (LUHMES) cells into human dopaminergic-like neurons and found that LCN2 mRNA was progressively induced in mouse brain after the intrastriatal transplantation of human dopaminergic-like neurons. The induction of LCN2 protein was detected in a subset of astrocytes and neutrophils infiltrating the core of the engrafted sites, but not in neurons and microglia. LCN2-immunoreactive astrocytes within the engrafted sites expressed lower levels of A1 and A2 astrocytic markers. Recruitment of microglia, neutrophils, and monocytes after transplantation was attenuated in LCN2 deficiency mice. The expression of M2 microglial markers was significantly elevated and survival of engrafted neurons was markedly improved after transplantation in LCN2 deficiency mice. BOCT, the cell surface receptor for LCN2, was induced in dopaminergic-like neurons after differentiation, and treatment with recombinant LCN2 protein directly induced apoptosis in dopaminergic-like neurons in a dose-dependent manner. These findings suggested that LCN2 is a neurotoxic factor for the engrafted neurons and a modulator of neuroinflammation, and LCN2 inhibition may be useful in reducing rejection after neural transplantation.

Citation: Weng, YC; Huang, YT; Chiang, IC; Tsai, PJ; Su, YW; Chou, WH. Lipocalin-2 mediates the rejection of neural transplants. The FASEB Journal. 2021 Feb;35(2):Article number e21317

 

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