Anti-inflammatory response following uptake of apoptotic bodies by meningothelial cells

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JOURNAL OF NEUROINFLAMMATION

RESEARCH

Open Access

Anti-inflammatory response following uptake of apoptotic bodies by meningothelial cells Jia Li1,2, Lei Fang1, Peter Meyer1,3, Hanspeter E Killer4, Josef Flammer3 and Albert Neutzner1,3*

Abstract Background: Meningothelial cells (MECs) are the cellular components of the meninges. As such, they provide important barrier function for the central nervous system (CNS) building the interface between neuronal tissue and the cerebrospinal fluid (CSF), and are also part of the immune response of the CNS. Methods: Human, immortalized MECs were analyzed by flow cytometry and confocal microscopy to study the uptake of apoptotic cells. Furthermore, cytokine and chemokine production by MECs was analyzed by cytokine array and ELISA. Results: We found that MECs are highly active phagocytes able of ingesting and digesting large amounts of apoptotic cells. Furthermore, the uptake of apoptotic cells by MECs was immune suppressive via inhibiting the secretion of pro-inflammatory and chemoattractant cytokines and chemokines IL-6, IL-8, IL-16, MIF, and CXCL1, while increasing the secretion of anti-inflammatory IL-1 receptor antagonist by MECs. Conclusion: MECs respond with the secretion of anti-inflammatory cytokines and chemokines following the uptake of apoptotic cells potentially connecting these cells to processes important for the shut-down of immune responses in the brain. Keywords: Meningothelial cells, Apoptotic cells, Cytokines, Cerebrospinal fluid, Central nervous system, Optic nerve

Introduction The central nervous system (CNS) is enveloped by a complex layered structure, the meninges, providing protection from outside influence. The meninges comprise dura mater and the leptomeninges, which consist of the arachnoid mater and pia mater together with the trabeculae and septae that traverse the cerebrospinal fluid (CSF-)filled subarachnoidal space [1,2]. The cellular component of the pia, arachnoid, and the trabeculae and septae of the subarachnoidal space are meningothelial cells (MECs) also referred to as leptomeningeal cells [3]. MECs form a monolayer and are connected via tight junctions, gap junctions, and desmosomes contributing as part of the pia mater to the barrier between the CSF and the neuronal tissue [4]. Recent work by us and others revealed several functions of MECs beyond their function as cells simply covering neuronal tissue. MECs were shown to be actively involved * Correspondence: [email protected] 1 Department of Biomedicine, University Basel, Basel, Switzerland 3 Department of Ophthalmology, University Basel, Basel, Switzerland Full list of author information is available at the end of the article

in physiological and pathophysiological processes in the subarachnoidal space and in the CSF compartment [5-7]. Namely, MECs were shown to influence subarachnoidal architecture during glaucomatous neurodegeneration through increased proliferation [8] and to modulate CSF composition under pathological conditions through the production of lipocalin-type