IFN-gamma-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments
Vardjan, Nina (Author), Burger, Anže (Author), Potokar, Maja (Author), Švajger, Urban (Author), Kreft, Marko (Author), Jeras, Matjaž (Author), De Pablo, Yolanda (Author), Faiz, Maryam (Author), Pekny, Milos (Author), Zorec, Robert (Author)

URLURL - Presentation file, Visit http://www.jneuroinflammation.com/content/pdf/1742-2094-9-144.pdf This link opens in a new window

In immune-mediated diseases of the central nervous system, astrocytes exposed to interferon-gama (IFN-gama) can express major histocompatibility complex (MHC) class II molecules and antigens on their surface. MHC class II molecules are thought to be delivered to the cell surface by membrane-bound vesicles. However, the characteristics and dynamics of this vesicular traffic are unclear, particularly in reactive astrocytes, which overexpress intermediate filament (IF) proteins that may affect trafficking. The aim of this study was to determine the mobility of MHC class II vesicles in wild-type (WT) astrocytes and in astrocytes devoid of IFs. Methods The identity of MHC class II compartments in WT and IF-deficient astrocytes 48 h after IFN- Ž activationwas determined immunocytochemically by using confocal microscopy. Timelapse confocal imaging and Alexa Fluor546-dextran labeling of late endosomes/lysosomes in IFN-gama treated cells was used to characterize the motion of MHC class II vesicles. The mobility of vesicles was analyzed using Particle TR software. Results Confocal imaging of primary cultures of WT and IF-deficient astrocytes revealed IFN-Ž induced MHC class II expression in late endosomes/lysosomes, which were specifically labeled with Alexa Fluor546-conjugated dextran. Live imaging revealed faster movement of dextran-positive vesicles in IFN-Ž-treated than in untreated astrocytes. Vesicle mobility was lower in IFN-gama-treated IF-deficient astrocytes than in WT astrocytes. Thus, the IFN-gama-induced increase in the mobility of MHC class II compartments is IF-dependent. Conclusions Since reactivity of astrocytes isa hallmark of many CNS pathologies, it is likely that the upregulation of IFs under such conditions allows a faster and therefore a more efficient delivery of MHC class II molecules to the cell surface. In vivo, such regulatory mechanisms may enable antigen-presenting reactive astrocytes to respond rapidly and in a controlled manner to CNS inflammation.

Keywords:astrocytes, vesicle mobility, late endosomes/lysosomes, major histocompatibility class II compartments, interferon-gamma, dextran labeling, immune response
Work type:Not categorized (r6)
Tipology:1.01 - Original Scientific Article
Organization:FFA - Faculty of Pharmacy
Number of pages:13 str.
Numbering:Vol. 9, art. no. 144
ISSN on article:1742-2094
DOI:10.1186/1742-2094-9-144 Link is opened in a new window
COBISS.SI-ID:3272561 Link is opened in a new window
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Record is a part of a journal

Title:Journal of neuroinflammation
Shortened title:J. neuroinflamm.
Publisher:BioMed Central.
COBISS.SI-ID:513966617 This link opens in a new window

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