Air pollution as a contributor to the inflammatory activity of multiple sclerosis

Journal of Neuroinflammation

Luca Lova¹  Andrea Cortese²  Giulia Mallucci³  Alfredo Romani⁴  Silvia Villa⁴  Roberto Bergamaschi⁴  Diego Franciotta⁴  Sabrina La Salvia⁴  Cristina Cereda⁴  Giuseppe Quartuccio⁵  Patrizia Comoli⁵  Ilaria Guido⁵  Sabrina Basso⁵  Luca Battistini⁶  Elisabetta Volpe⁶  Valentina Bollati⁷ 

[1] Biosciences S.p.A., Milan, Italy;Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy;Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, Queen Square, London, UK;Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy;IRCCS Mondino Foundation, Pavia, Italy;IRCCS Mondino Foundation, Pavia, Italy;IRCCS Policlinico S. Matteo Foundation, Pavia, Italy;IRCCS Santa Lucia Foundation, Rome, Italy;University of Milan, Milan, Italy;

关键词: Air pollution;    Particulate matter;    Multiple sclerosis;    Th 17 lymphocytes;    Adhesion molecules;   

DOI  :  10.1186/s12974-020-01977-0

来源: Springer

【 摘 要 】

ObjectiveAir pollution has been recently identified as a risk factor for multiple sclerosis. Aim of this study was to investigate the immunological mechanism underlying the clinical association between air pollution, namely exposure to particulate matter 10 (PM10), and inflammatory activity of multiple sclerosis (MS)MethodsDaily recording of PM10 was obtained by monitors depending on the residence of subjects. Expression of molecules involved in activation, adhesion, and migration of T lymphocytes were tested by flow cytometry in 57 MS patients and 19 healthy controls. We next assessed in vitro the effect of PM10 on expression of C-C chemokine receptors 6 (CCR6) by peripheral blood mononuclear cells (PBMCs), on cytokine production by monocyte-derived dendritic cells (mdDC), and on T cell polarization in PBMC/mdDC mixed cultures.ResultsWe identified a significant correlation between mean PM10 levels and expression of CCR6 CD4+ T circulating cells in MS patients. This was paralleled by the observation in vitro of a higher level of CCR6 expression on PBMC following treatment with increased doses of particulate matter. Moreover, in mdDC cultures, particulate matter induced the secretion by mdDC of Th17 polarizing IL1 beta, IL6, and IL23 and, in mdDC/PBMC mixed cultures, enhanced generation of IL17-producing T cells.ConclusionsEx vivo and in vitro studies support the pro-inflammatory role of PM in MS, by upregulating expression of CCR6 on circulating CD4+ T cells and inducing in innate immune cells the production of Th17 polarizing cytokines. Therefore, we speculate that in MS respiratory exposure to PM10 may induce the production in the lung of autoreactive Th17 lymphocytes and boost their migratory properties through the blood-brain barrier.

【 授权许可】

CC BY