Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity

Abstract

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.

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“…DA rats were not investigated in their study, but we were able to convincingly demonstrate that these rats are also highly susceptible to CFA-free EAE ( 66 – 68 ). Classically, EAE in DA rats is induced with SCH (either guinea pig or rat) emulsified in CFA ( 69 – 71 ).…”

“…The incidence higher than 90% and the clinical course that is prolonged in comparison to SCH + CFA immunization was determined in DA rats immunized with SCH ( 67 ). Infiltrates were observed in both the white and the gray matter of the spinal cord and also in the brain ( 68 ). This model has proven useful for evaluating the therapeutic efficacy of novel agents ( 73 , 74 ).…”