Tai-June Yoo, M.D., Ph.D.
Departments of Medicine and Microbiology
The University of Tennessee Health Science Center
Department of Medicine - Allergy/Immunology
Memphis, TN 38163
Phone: (901) 448-6663
Fax: (901) 448-5854
Email: Tai-June Yoo, M.D.
- M.D. Institution: Seoul National School of Medicine, Seoul, Korea
- Ph.D. Institution: University of California, Berkeley, Department of Biophysics
This laboratory studies the basic molecular and immune mechanisms of pathogenic processes affecting auditory function. We also focus on the immune mechanism of other related autoimmune diseases: experimental autoimmune encephalomyelitis (EAE).
We have found that if persons with a HLA A1/B8 DR3 haplotype have a positive type II collagen antibody, there is a relative risk factor of eight that they have autoimmune ear disease. We have found that 57% of sera from ear disease patients had antibodies that bound type II collagen, 62% had antibodies that bound type IX collagen and that three out of six patients with Meniere's disease with hearing loss had antibody binding activity with 30 Kd, a previously non-reported protein from the labyrinthine membrane and from human cochlear tissue extract. Further characterization of this 30 Kd protein is in progress.
We have an animal model that mimics certain aspects of collagen induced human autoimmune ear disease. When rodents are immunized with type II collagen, they develop hearing impairment as well as arthritis. However, the onset time of these diseases is different; arthritis develops first, then hearing impairment. In both cases, a higher titer of autoantibody was identified. The usage of Vk gene segments is restricted in those anti-type II collagen antibodies. It is of interest to note that the usage of TCR V regions are restricted to certain V gene subfamilies in both diseases. At this moment, whether same subsets of TCR gene(s) are used by T cells involved in these two diseases is unclear. The transfer of anti-type II collagen antibody or type II collagen specific T cells could pass these diseases to naive mice. These results suggest that collagen-induced autoimmune diseases are mediated by B cells as well as T cells.
We discovered that the shiverer mice, which have partial deletion of MBP gene, have hearing impairment. However, transgenic transfer of the wild type MBP gene back to the shiverer mice restored hearing to near normal levels. This is the first gene therapy study in the autoimmune ear disease field.
Experimental allergic encephalomyelitis (EAE), a T cell mediated central nervous system disease, has been described elsewhere. The results from our and other laboratories have found that TCR Valpha and/or Vb are restricted in H-2u and H-2s background mice. It is of interest to note that the MBP specific T cell V-region usage pattern is influenced strongly by the repertoire of available germline segments; segments that are used in some strains of mice are suppressed if alternative segments are available in hybrid mice. Our results suggest that this disease is linked to hearing impairment. Whether the same TCR are involved in the encephalomyelitis and ear disease is under investigation. These results confirmed the gene therapy as described in the shiverer mice.
We have created several lines of transgenic mice to study in vivo the auto immune diseases, CIA, EAE, and CIAED. Specifically, we are interested in the contribution of g-interferon (g-IFN) to the induction, maintenance, and pathogenesis of autoimmune ear diseases. It has been shown that injection of g-IFN aggravates the disease progress in CIA and EAE. We feel that transgenic mice with g-IFN expression localized to the affected tissue might, therefore, shed light on some aspects of the disease progress. However, all the transgenic mice were completely normal in growth, appearance, and healthy. FACS analysis of F1 CII-transgenic mice revealed normal ratios of CD4-CD8+, CD4+, CD8+, and CD4-CD8 cells. Further experiments are in progress to solve this mystery.
- Zhou B, Yuan J, Zhou Y, Yang J, James AW, Nair U, Shu X, Liu W, Kanangat S, Yoo TJ. The attenuation of cockroach allergy by DNA vaccine encoding cockroach allergen Bla g 2. Cell Immunol. 2012 Jul-Aug;278(1-2):120-4. doi: 10.1016/j.cellimm.2012.05.015. Epub 2012 Jun 7. PubMed PMID: 22960278.
- Zhou B, Ensell M, Zhou Y, Nair U, Glickstein J, Kermany MH, Cai Q, Cai C, Liu W, Deng YP, Kakigi A, Barbieri M, Mora M, Kanangat S, Yoo TJ. Prevention and treatment of DNA vaccine encoding cockroach allergen Bla g 1 in a mouse model of allergic airway inflammation. Allergy. 2012 Feb;67(2):166-74. doi: 10.1111/j.1398-9995.2011.02727.x. Epub 2011 Sep 29. PubMed PMID: 21958323.
- Zhou B, Yuan J, Zhou Y, Ghawji M Jr, Deng YP, Lee AJ, Lee AJ, Nair U, Kang AH, Brand DD, Yoo TJ. Administering human adipose-derived mesenchymal stem cells to prevent and treat experimental arthritis. Clin Immunol. 2011 Dec;141(3):328-37. doi: 10.1016/j.clim.2011.08.014. Epub 2011 Sep 2. PubMed PMID: 21944669.
- Zhou B, Kermany MH, Cai Q, Cai C, Zhou Y, Nair U, Liu W, Yoo TJ. Experimental autoimmune hearing loss is exacerbated in IL-10-deficient mice and reversed by IL-10 gene transfer. Gene Ther. 2012 Feb;19(2):228-35. doi: 10.1038/gt.2011.88. Epub 2011 Jun 23. PubMed PMID: 21697956.
- Zhou Y, Yuan J, Zhou B, Lee AJ, Lee AJ, Ghawji M Jr, Yoo TJ. The therapeutic efficacy of human adipose tissue-derived mesenchymal stem cells on experimental autoimmune hearing loss in mice. Immunology. 2011 May;133(1):133-40. doi: 10.1111/j.1365-2567.2011.03421.x. Epub 2011 Mar 2. PubMed PMID: 21366561; PubMed Central PMCID: PMC3088975.
- Zhou B, Kermany MH, Glickstein J, Cai Q, Cai C, Zhou Y, Nair U, Kim JW, Kim P, Liu W, Kanangat S, Yoo TJ. Murine autoimmune hearing loss mediated by CD4+ T cells specific for β-tubulin. Clin Immunol. 2011 Feb;138(2):222-30. doi: 10.1016/j.clim.2010.11.007. Epub 2010 Dec 9. PubMed PMID: 21145286.