Experimental autoimmune hearing loss is exacerbated in IL-10-deficient mice and reversed by IL-10 gene transfer

B. Zhou, M. H. Kermany, Q. Cai, Chun Cai, Y. Zhou, U. Nair, W. Liu, T. J. Yoo

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)228-235
Number of pages8
JournalGene Therapy
Volume19
Issue number2
DOIs
StatePublished - Feb 1 2012

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Hearing Loss
Interleukin-10
Genes
Regulatory T-Lymphocytes
Tubulin
Hearing
T-Lymphocytes
Th1 Cells
Wild Animals
Brain Stem Auditory Evoked Potentials
Alopecia
Interferons

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Experimental autoimmune hearing loss is exacerbated in IL-10-deficient mice and reversed by IL-10 gene transfer. / Zhou, B.; Kermany, M. H.; Cai, Q.; Cai, Chun; Zhou, Y.; Nair, U.; Liu, W.; Yoo, T. J.

In: Gene Therapy, Vol. 19, No. 2, 01.02.2012, p. 228-235.

Research output: Contribution to journalArticle

Zhou, B. ; Kermany, M. H. ; Cai, Q. ; Cai, Chun ; Zhou, Y. ; Nair, U. ; Liu, W. ; Yoo, T. J. / Experimental autoimmune hearing loss is exacerbated in IL-10-deficient mice and reversed by IL-10 gene transfer. In: Gene Therapy. 2012 ; Vol. 19, No. 2. pp. 228-235.
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