Transplantation of CTLA4Ig gene-transduced adipose tissue-derived mesenchymal stem cells reduces inflammatory immune response and improves Th1/Th2 balance in experimental autoimmune thyroiditis.
BACKGROUND
Autoimmune thyroiditis is one of common organ-specific autoimmune disease. The aim of this study was to observe the effect of adipose tissue derived mesenchymal stem cells (ATMSC) and CTLA4Ig gene-transduced ATMSC on autoimmune thyroiditis.


METHODS
Experimental autoimmune thyroiditis was induced by immunization with thyroglobulin. Animals were divided into three groups: (i) a half million of human ATMSC, (ii) a half million of murine CLTA4Ig gene-transduced human ATMSC (CTLA4Ig-MSC), or (iii) normal saline (as control), which were administered intravenously four times within a 3-week period. Blood and tissue samples were collected 1 week after the last cell transplantation.


RESULTS
The absorbance of serum thyroglobulin autoantibody (TgAA) in the CTLA4Ig-MSC group was considerably lower than those in other groups. In culture supernatant of LPS-stimulated spleen cells, both of the MSC-treated groups showed significantly lower absorbances of TgAA than the control. Flow cytometric analysis of spleen cells revealed a significant decrease in the proportion of CD3+ and CD11b in the CTLA4Ig-MSC group compared to the other groups. Lymphocyte infiltration in the thyroid glands was also dramatically decreased in both of MSC-treated groups. Cytokine analysis showed that ATMSC decreased the production of proinflammatory cytokines and improved the Th1/Th2 balance by down-regulating Th1 cytokines.


CONCLUSIONS
Although CTLA4Ig-MSC transplantation had better result in reduction of serum TgAA, both of ATMSC and CTLA4Ig-MSC transplantations are promising treatments for autoimmune thyroiditis judging from the results of histopathology and cytokine analysis. They may be attractive candidates for treating organ-specific autoimmune disease.
Laboratory Animal Research Center, Samsung Biomedical Research Institute, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea. vet.cew@gmail.com
Eun Wha
EW
Choi
Il Seob
IS
Shin
Hee Woo
HW
Lee
So Young
SY
Park
Ji Hyun
JH
Park
Mi Hyun
MH
Nam
Jong Sung
JS
Kim
Sang Kyu
SK
Woo
Eun Ji
EJ
Yoon
Sung Keun
SK
Kang
Jeong Chan
JC
Ra
Hwa Young
HY
Youn
Sung Hwa
SH
Hong
D000069594:Abatacept; D000273:Adipose Tissue / Q000166:cytology / Q000637:transplantation; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007249:Inflammation / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000628:therapy*; D014161:Transduction, Genetic
D001323:Autoantibodies; D016207:Cytokines; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; C006606:anti-thyroglobulin; D000069594:Abatacept