Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity
2024
Authors:
Lazarević, MilicaStegnjaić, Goran
Jevtić, Bojan
Despotović, Sanja
Ignjatović, Đurđica
Stanisavljević, Suzana
Nikolovski, Neda
Momčilović, Miljana
Fraser, Graeme L
Dimitrijević, Mirjana
Miljković, Đorđe
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
Experimental autoimmune encephalomyelitis (EAE) induced in inbred rodents, i.e., genetically identical animals kept under identical environmental conditions, shows variable clinical outcomes. We investigated such variations of EAE in Dark Agouti rats immunized with spinal cord homogenate and identified four groups: lethal, severe, moderate, and mild, at day 28 post immunization. Higher numbers of CD4+ T cells, helper T cells type 1 (Th1) and 17 (Th17) in particular, were detected in the spinal cord of the severe group in comparison with the moderate group. In addition, increased proportion of Th1 and Th17 cells, and heightened levels of interferon (IFN)-γ and interleukin (IL)-6 were detected in the small intestine lamina propria of the severe group. A selective agonist of free fatty acid receptor type 2 (Ffar2) applied orally in the inductive phase of EAE shifted the distribution of the disease outcomes towards milder forms. This effect was paralleled with potentiation of intestinal innate lymphoid cells type 3 (ILC3) regulatory properties, and diminished Th1 and Th17 cell response in the lymph nodes draining the site of immunization. Our results suggest that different clinical outcomes in DA rats are under determinative influence of intestinal ILC3 activity during the inductive phase of EAE.
Keywords:
experimental autoimmune encephalomyelitis; multiple sclerosis; intestine; T cells; innate lymphoid cells; free fatty acid receptor type 2Source:
Journal of Neuroinflammation, 2024, 21, 26-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
DOI: 10.1186/s12974-024-03017-7
ISSN: 1742-2094
PubMed: 38238790