HLA Class II Polymorphisms Modulate Gut Microbiota and Experimental Autoimmune Encephalomyelitis Phenotype.

Autor: Shahi SK; Department of Pathology, University of Iowa, Iowa City, IA., Ali S; Department of Pathology, University of Iowa, Iowa City, IA.; Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA., Jaime CM; Department of Pathology, University of Iowa, Iowa City, IA., Guseva NV; Department of Pathology, University of Iowa, Iowa City, IA., Mangalam AK; Department of Pathology, University of Iowa, Iowa City, IA; ashutosh-mangalam@uiowa.edu.; Graduate Program in Immunology, University of Iowa, Iowa City, IA; and.; Graduate Program in Molecular Medicine, University of Iowa, Iowa City, IA.
Jazyk: angličtina
Zdroj: ImmunoHorizons [Immunohorizons] 2021 Aug 11; Vol. 5 (8), pp. 627-646. Date of Electronic Publication: 2021 Aug 11.
DOI: 10.4049/immunohorizons.2100024
Abstrakt: Multiple sclerosis (MS) is an autoimmune disease of the CNS in which the interaction between genetic and environmental factors plays an important role in disease pathogenesis. Although environmental factors account for 70% of disease risk, the exact environmental factors associated with MS are unknown. Recently, gut microbiota has emerged as a potential missing environmental factor linked with the pathobiology of MS. Yet, how genetic factors, such as HLA class II gene(s), interact with gut microbiota and influence MS is unclear. In the current study, we investigated whether HLA class II genes that regulate experimental autoimmune encephalomyelitis (EAE) and MS susceptibility also influence gut microbiota. Previously, we have shown that HLA-DR3 transgenic mice lacking endogenous mouse class II genes (AE-KO) were susceptible to myelin proteolipid protein ( 91-110 )-induced EAE, an animal model of MS, whereas AE-KO.HLA-DQ8 transgenic mice were resistant. Surprisingly, HLA-DR3.DQ8 double transgenic mice showed higher disease prevalence and severity compared with HLA-DR3 mice. Gut microbiota analysis showed that HLA-DR3, HLA-DQ8, and HLA-DR3.DQ8 double transgenic mice microbiota are compositionally different from AE-KO mice. Within HLA class II transgenic mice, the microbiota of HLA-DQ8 mice were more similar to HLA-DR3.DQ8 than HLA-DR3. As the presence of DQ8 on an HLA-DR3 background increases disease severity, our data suggests that HLA-DQ8-specific microbiota may contribute to disease severity in HLA-DR3.DQ8 mice. Altogether, our study provides evidence that the HLA-DR and -DQ genes linked to specific gut microbiota contribute to EAE susceptibility or resistance in a transgenic animal model of MS.
(Copyright © 2021 The Authors.)
Databáze: MEDLINE
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