title: Experimental autoimmune hearing loss is exacerbated in IL-10-deficient mice and reversed by IL-10 gene transfer.
abstract: Interleukin-10 (IL-10) has an important role in the homeostatic regulation of autoreactive T-cell repertoire. We hypothesized that endogenous IL-10 would regulate the severity of β-tubulin-induced experimental autoimmune hearing loss (EAHL) and that exogenous IL-10 would abrogate it. BALB/c wild-type (WT) and homozygous IL-10-deficient mice (IL-10(-/-)) underwent β-tubulin immunization to develop EAHL; some IL-10 mice with EAHL were administered IL-10 DNA at the peak of EAHL. Auditory brainstem responses were examined over time. EAHL developed progressively in both WT and IL-10(-/-) mice. However, the severity of hearing loss in the IL-10(-/-) mice was significantly greater than that in WT animals. Moreover, disease severity was associated with a significantly enhanced interferon-γ level and loss of hair cells in IL-10(-/-) mice. IL-10 administered to EAHL IL-10(-/-) mice promoted IL-10 expression. Consequently, hearing significantly improved by protecting hair cells in established EAHL. Importantly, IL-10 treatment suppressed proliferation of antigen-specific T-helper type 1 (Th1) cells, and the suppression can be attributed to inducing IL-10-secreting regulatory T cells that suppressed autoreactive T cells. We demonstrated that the lack of IL-10 exacerbated hearing loss, and the exogenous administration of IL-10 improved hearing. Mechanistically, our results indicate that IL-10 is capable of controlling autoimmune reaction severity by suppressing Th1-type proinflammatory responses and inducing IL-10-secreting regulatory T cells.
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: B
authors.initials: B
authors.lastname: Zhou
authors.forename: M H
authors.initials: MH
authors.lastname: Kermany
authors.forename: Q
authors.initials: Q
authors.lastname: Cai
authors.forename: C
authors.initials: C
authors.lastname: Cai
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: U
authors.initials: U
authors.lastname: Nair
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: T J
authors.initials: TJ
authors.lastname: Yoo
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D034381:Hearing Loss / Q000139:chemically induced* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014404:Tubulin / Q000008:administration & dosage / Q000276:immunology
chemical_list: C556062:IL10 protein, mouse; D014404:Tubulin; D016753:Interleukin-10; D007371:Interferon-gamma