Immunology
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/30441
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Browsing Immunology by Author "Oh, Jiyoung"
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Item Age-related thymic atrophy impairs development and function of an antigen-specific tTreg clone(2021) Thomas, Rachel; Oh, Jiyoung; Wang, Weikan; Su, DongmingPurpose: The atrophied thymus generates an increased ratio of polyclonal thymic Regulatory T (tTreg) cells to thymic conventional T (tTcon) cells, and peripheral Treg (pTreg) cells accumulate during aging. So, why are pTregs in the elderly unable to effectively suppress age-related inflammation ("inflammaging")? Methods: We utilized a mock self-antigen (autoimmune pancreatitis) chimeric mouse model, in which irradiated rat insulin promotor (RIP)-driven mOVA mice received mixed OT-II TCR transgenic and wild-type bone marrow. Thus, we can easily visualize the generation and activation of an antigen-specific Treg cell clone. Additionally, our mOVA mice carry a FoxN1-floxed gene for induction of conditional thymic atrophy, analogous to the aged thymus. Results: The chimeric mice with thymic atrophy exhibited significant decline in central and peripheral OVA-specific (OT-II) Tregs, but not total (pan) Tregs. Further, intrinsic Treg changes in FoxP3 expression was observed, suggestive of reduced suppressive capacity. This was confirmed via functional assays showing that OVA-specific Tregs were significantly less able to suppress antigen-specific stimulation of Teffs in vitro. Additionally, we performed TCR sequencing and observed a trend for decreased TCR diversity in tTregs in mice with thymic atrophy. Conclusion: These data indicate that although the effects of age-related thymic atrophy do not affect pan-Treg generation, certain tissue-specific Treg clones may experience abnormal thymic selection, creating holes in Treg-mediated immunoregulation. This, combined with enhanced pan-pTreg cells, may help explain inflammaging.Item Roles of aging-associated Treg cell accumulation in experimental autoimmune encephalomyelitis (EAE) — a model of late-onset multiple sclerosis (MS)(2021) Wang, Weikan; Thomas, Rachel; Oh, Jiyoung; Su, DongmingPurpose: MS, a T cell-mediated autoimmune demyelinating disease of the central nervous system (CNS), has not been sufficiently studied in the elderly, despite instances of late-onset MS. Regulatory T (Treg) cells play an ameliorative role in MS. Given that the aged immune system exhibits accumulated peripheral Treg (pTreg) cells, the role of Treg cell in aged MS patients remains to be elucidated. Methods: We immunized young and aged mice to induce EAE and investigated the disease courses and Treg cell associated mechanisms. Results: We found that the aged mice have two types of late-onset EAE. In Type I, EAE onset was delayed in the age mice, but the disease became more severe once after onset; Alternatively, in type II, some aged mice never developed into as severe symptoms as the young mice until a second antigen challenge was given, which led to more progressive disease courses than their young counterparts. This phenotype was potentially associated with a lower proportion of CNS-specific Treg cells in the aged CNS, even though the aged mice had a high proportion of polyclonal pTreg cells. Transient inhibition of polyclonal pTreg cells partially ameliorated the disease severity in the aged mice, accompanied with increased CNS-specific Treg cells in the CNS. Conclusions: Therefore, we suggest that accumulated polyclonal pTreg cells in the aged periphery are detrimental for CNS repair processes during neuronal inflammation in aged MS mice, potentially due to hampering trafficking of CNS-specific Treg cells into the CNS.