RISS 검색 - 국내학술지논문

무료
기관 내 무료
유료

내보내기
내책장담기
한글로보기

정확도순

내림차순

내림차순

10개씩 출력

1
Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism

Pan, Youdong,Tian, Tian,Park, Chang Ook,Lofftus, Serena Y.,Mei, Shenglin,Liu, Xing,Luo, Chi,O’Malley, John T.,Gehad, Ahmed,Teague, Jessica E.,Divito, Sherrie J.,Fuhlbrigge, Robert,Puigserver, Pere,Kru Macmillan Publishers Limited, part of Springer Nat 2017 Nature Vol.543 No.7644
- 원문보기
Tissue-resident memory T (TRM) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. However, the biological pathways that enable the long-term survival of TRM cells are obscure. Here we show that mouse CD8+ TRM cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). We further show that T-cell-specific deficiency of Fabp4 and Fabp5 (Fabp4/Fabp5) impairs exogenous free fatty acid (FFA) uptake by CD8+ TRM cells and greatly reduces their long-term survival in vivo, while having no effect on the survival of central memory T (TCM) cells in lymph nodes. In vitro, CD8+ TRM cells, but not CD8+ TCM cells, demonstrated increased mitochondrial oxidative metabolism in the presence of exogenous FFAs; this increase was not seen in Fabp4/Fabp5 double-knockout CD8+ TRM cells. The persistence of CD8+ TRM cells in the skin was strongly diminished by inhibition of mitochondrial FFA β-oxidation in vivo. Moreover, skin CD8+ TRM cells that lacked Fabp4/Fabp5 were less effective at protecting mice from cutaneous viral infection, and lung Fabp4/Fabp5 double-knockout CD8+ TRM cells generated by skin vaccinia virus (VACV) infection were less effective at protecting mice from a lethal pulmonary challenge with VACV. Consistent with the mouse data, increased FABP4 and FABP5 expression and enhanced extracellular FFA uptake were also demonstrated in human CD8+ TRM cells in normal and psoriatic skin. These results suggest that FABP4 and FABP5 have a critical role in the maintenance, longevity and function of CD8+ TRM cells, and suggest that CD8+ TRM cells use exogenous FFAs and their oxidative metabolism to persist in tissue and to mediate protective immunity.
2
Staged development of long-lived T-cell receptor αβ TH17 resident memory T-cell population to Candida albicans after skin infection

Park, Chang Ook,Fu, Xiujun,Jiang, Xiaodong,Pan, Youdong,Teague, Jessica E.,Collins, Nicholas,Tian, Tian,O'Malley, John T.,Emerson, Ryan O.,Kim, Ji Hye,Jung, Yookyung,Watanabe, Rei,Fuhlbrigge, Robert C Elsevier 2018 The Journal of allergy and clinical immunology Vol.142 No.2
- 원문보기
Background Candida albicans is a dimorphic fungus to which human subjects are exposed early in life, and by adulthood, it is part of the mycobiome of skin and other tissues. Neonatal skin lacks resident memory T (TRM) cells, but in adults the C albicans skin test is a surrogate for immunocompetence. Young adult mice raised under specific pathogen-free conditions are naive to C albicans and have been shown recently to have an immune system resembling that of neonatal human subjects. Objective We studied the evolution of the adaptive cutaneous immune response to Candida species. Methods We examined both human skin T cells and the de novo and memory immune responses in a mouse model of C albicans skin infection. Results In mice the initial IL-17–producing cells after C albicans infection were dermal γδ T cells, but by day 7, αβ TH17 effector T cells were predominant. By day 30, the majority of C albicans–reactive IL-17–producing T cells were CD4 TRM cells. Intravital microscopy showed that CD4 effector T cells were recruited to the site of primary infection and were highly motile 10 days after infection. Between 30 and 90 days after infection, these CD4 T cells became increasingly sessile, acquired expression of CD69 and CD103, and localized to the papillary dermis. These established TRM cells produced IL-17 on challenge, whereas motile migratory memory T cells did not. TRM cells rapidly clear an infectious challenge with C albicans more effectively than recirculating T cells, although both populations participate. We found that in normal human skin IL-17–producing CD4+ TRM cells that responded to C albicans in an MHC class II–restricted fashion could be identified readily. Conclusions These studies demonstrate that C albicans infection of skin preferentially generates CD4+ IL-17–producing TRM cells, which mediate durable protective immunity.

내보내기
내책장담기
한글로보기

정확도순

내림차순

내림차순

10개씩 출력

맨처음 페이지로 1 맨끝 페이지로

상세검색

RISS 보유자료

상세검색

해외전자자료

연관 검색어 추천