A potential role for the PD1/PD-L1 pathway in the neuroinflammation of Alzheimer%26apos;s disease

作者：Saresella Marina^*; Calabrese Elena; Marventano Ivana; Piancone Federica; Gatti Andrea; Farina Elisabetta; Alberoni Margherita; Clerici Mario

来源：Neurobiology of Aging, 2012, 33(3): 624.e11.

DOI：10.1016/j.neurobiolaging.2011.03.004

• Alzheimer%26apos
• s disease
• Inflammation
• Immunology
• Interleukin-10
• PD1
• PD-L1
• Apoptosis

The interaction between PD1 on T lymphocytes and PD-L1 on antigen presenting cells (APC) modulates the balance between inflammation and tolerance by inducing IL-10 production and apoptosis of antigen-specific cells. We analyzed the PD1/PD-L1 pathway, annexin V (AV)-expression, and proliferation in amyloid-beta (A beta)-stimulated PBMC of patients with Alzheimer%26apos;s disease (AD) (N = 35) or mild cognitive impairment (MCI) (N = 30) and of age-matched healthy controls (HC; N = 30). Results showed that PD1-expressing CD4(+) T cells, density of PD-L1 on CD14(+) APC, IL-10 production, and PD-L1-expressing/IL-10-producing CD14(+) APC were significantly reduced in AD and MCI patients compared to HC. A beta-stimulated PD1/AV-expressing (apoptotic) CD4(+) T cells were also diminished, whereas proliferation was augmented in AD and MCI patients compared to controls. Finally, incubation of cells with PD-L1-neutralizing antibodies significantly decreased apoptosis of A beta-specific CD4(+) T lymphocytes. An impairment of the PD-L1/PD1 pathway is present in AD and MCI. Such alteration results in reduced IL-10 production and diminished apoptosis of A beta-specific CD4(+) T lymphocytes; these phenomena could play a role in the neuroinflammation accompanying AD.

• 出版日期2012-3