Impaired IL-17 Production in Gut-Residing Immune Cells of 5xFAD Mice with Alzheimer’s Disease Pathology
2018
Autori:
Saksida, TamaraKoprivica, Ivan
Vujičić, Milica
Stošić-Grujičić, Stanislava
Perović, Milka
Kanazir, Selma
Stojanović, Ivana D.
Tip dokumenta:
Članak u časopisu (Objavljena verzija)
,
© 2018 - IOS Press and the authors.
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
Alzheimer's disease (AD) is characterized by accumulation of amyloid-β plaques that further promotes microglia-mediated neuroinflammatory responses and inflammation in the brain. Emerging data are revealing the relation between gut-associated lymphoid tissue (GALT) cells and CNS, as effector cells primed in the gut might home to the brain. This study aimed to determine cell composition of GALT in 5xFAD mice, an established model for AD. Immune cells isolated from Peyer's patches (PP) and mesenteric lymph nodes (MLN) were stained with surface and intracellular markers for T helper (Th) subpopulations, B lymphocytes and macrophages and analyzed cytofluorimetrically, while cytokine expression and production were determined by qPCR and ELISA, respectively. Inflammation was detected in GALT of 5xFAD mice with established AD pathology. Although the production of IFN-γ, IL-4, and IL-10 was comparable between the strains, lower IL-17 production was observed in PP and MLN cells. This phenomenon could not be attributed to a lower abundance of Th17 cells, or cytokines that initiate their formation or propagation (TGF-β, IL-6, and IL-23). Also, reduced IL-17 production was not a consequence of altered Il-17 mRNA transcription or deficiency of Rorγt, a key transcription factor for IL-17. However, the expression of miR-155 (a non-coding micro RNA that promotes the development of Th17 cells), was significantly lower in MLN cells of 5xFAD mice. In contrast, mice without AD neuropathology did not have inflammation in GALT or altered Th17 numbers, nor decreased IL-17 production. In conclusion, the observed changes in GALT of 5xFAD mice mirror the disease progression and might reflect inadequate immune surveillance in the gut and lead to enhanced AD pathology.
Ključne reči:
5xFAD mice; IL-17; Peyer’s patches; Amyloid-β; Mesenteric lymph nodesIzvor:
Journal of Alzheimer's disease : JAD, 2018, 61, 2, 619-630Finansiranje / projekti:
- Plastičnost mozga tokom starenja: uticaj dijetalne restrikcije i anestezije (RS-MESTD-Basic Research (BR or ON)-173056)
- Molekularni mehanizmi fiziološke i farmakološke kontrole inflamacije i kancera (RS-MESTD-Basic Research (BR or ON)-173013)
- National Institutes of Health (1R03AG046216)
DOI: 10.3233/JAD-170538
ISSN: 1387-2877
PubMed: 29254086