Neonatal-derived IL-17 producing dermal gammadelta T cells are required to prevent spontaneous atopic dermatitis

Atopic Dermatitis (AD) is a T cell-mediated chronic skin disease and is associated with altered skin barrier integrity. Infants with mutations in genes involved in tissue barrier fitness are predisposed towards inflammatory diseases, but most do not develop or sustain the diseases, suggesting that there exist regulatory immune mechanisms to prevent aberrant inflammation. The absence of one single murine dermal cell type, the innate neonatal-derived IL-17 producing gammadelta T (Tgammadelta17) cells, from birth resulted in spontaneous, highly penetrant AD with many of the major hallmarks of human AD. In Tgammadelta17 cell-deficient mice, basal keratinocyte transcriptome was altered months in advance of AD induction. Tgammadelta17 cells respond to skin commensal bacteria and the fulminant disease in their absence was driven by skin commensal bacteria dysbiosis. AD in this model was characterized by highly expanded dermal alphabeta T clonotypes that produce the type three cytokines, IL-17 and IL-22. These results demonstrate that neonatal Tgammadelta17 cells are innate skin regulatory T cells that are critical for skin homeostasis, and that IL-17 has dual homeostatic and inflammatory function in the skin

Indelible Footprints in Macau

This work is financed by national funds through FCT - Foundation for Science and Technology, I.P, in the scope of the projects UIDB/04311/2020 and UIDP/04311/2020. | Este trabalho é financiado por fundos nacionais através da FCT – Fundação para a Ciência e a Tecnologia, I.P., no âmbito dos projetos UIDB/04311/2020 e UIDP/04311/2020.The former Portuguese-ruled Macau has been a multi-ethnic/national rendezvous attracting people from different origins and serving as a stage for them to perform manifold roles. Through time, countless Chinese and foreign people have left indelible footprints along with the rendition of its disparate “visages”. This speck of land was once a religious bastion for the propagation of Christianity, a springboard for adventurers, and a haven for pirates and fugitives. It was also an opium depot, a slave trade centre, a gambling hotbed, and not least, an arena for the Sino-Portuguese power struggle. Yet, at times it was a sanctuary for the destitute, and a permanent shelter for the displaced. This book throws light on remarkable midway sojourners, whose significant presence was imprinted in history even though they appeared in Macau briefly for various purposes in the midst of cataclysmic vicissitudes in China. Central to the discussion are an invincible pirate king, an ardent anti-opium statesman, a reformist gentry-merchant, an impoverished musician, and a diasporized educationalist. Likewise, two controversial historians, a high-handed colonial governor, and a revengeful colonel stamped their abiding marks at a specific time in the colony’s history. Inextricably entwined with Macau’s socio-political evolution, some of these personages have contributed to the rich culture of this bewitching city.Macau, território que esteve sob governo português, tem sido um espaço de encontro multi-étnico/nacional, que atrai pessoas de diferentes origens e serve de palco para que desempenhem múltiplos papéis. Ao longo do tempo, inúmeros chineses e estrangeiros têm deixado pegadas indeléveis, juntamente com interpretação das suas díspares "faces". Esta mancha de terra foi em tempos um bastião religioso para a propagação do cristianismo, um trampolim para aventureiros e um refúgio para piratas e fugitivos. Era também um depósito de ópio, um centro de comércio de escravos, um ninho de jogo, e não menos importante, uma arena para a luta sino-portuguesa pelo poder. No entanto, por vezes, era um santuário para os indigentes e um abrigo permanente para os deslocados. Este livro lança luz sobre notáveis peregrinos a meio caminho, cuja presença significativa foi impressa na história, apesar de terem aparecido brevemente em Macau para vários fins no meio de vicissitudes cataclísmicas na China. No centro da discussão, encontram-se um rei pirata invencível, um ardente estadista anti-ópio, um reformador mercador aristocrata, um músico empobrecido e um pedagogo diáspora. Do mesmo modo, dois historiadores controversos, um governador colonial de mão pesada, e um coronel vingativo carimbaram as suas marcas permanentes num momento específico da história da colónia. Inextricavelmente ligados à evolução sociopolítica de Macau, alguns destes personagens contribuíram para a rica cultura desta cidade enfeitiçante.info:eu-repo/semantics/publishedVersio

Postmodernism: art and architecture in Hong Kong

published_or_final_versionLiterary StudiesMasterMaster of Art

Macau: a cultural janus in colonial vicissitudes

published_or_final_versionComparative LiteratureDoctoralDoctor of Philosoph

CD28 and ITK signals regulate autoreactive T cell trafficking

Activation of self-reactive T cells and their trafficking to target tissues leads to autoimmune organ destruction. Mice lacking the co-inhibitory receptor cytotoxic T lymphocyte antigen-4 (CTLA-4) develop fatal autoimmunity characterized by lymphocytic infiltration into nonlymphoid tissues. Here, we demonstrate that the CD28 co-stimulatory pathway regulates the trafficking of self-reactive Ctla4(-/-) T cells to tissues. Concurrent ablation of the CD28-activated Tec family kinase ITK does not block spontaneous T cell activation but instead causes self-reactive Ctla4(-/-) T cells to accumulate in secondary lymphoid organs. Despite excessive spontaneous T cell activation and proliferation in lymphoid organs, Itk(-/-); Ctla4(-/-) mice are otherwise healthy, mount antiviral immune responses and exhibit a long lifespan. We propose that ITK specifically licenses autoreactive T cells to enter tissues to mount destructive immune responses. Notably, ITK inhibitors mimic the null mutant phenotype and also prevent pancreatic islet infiltration by diabetogenic T cells in mouse models of type 1 diabetes, highlighting their potential utility for the treatment of human autoimmune disorders

PRC1 contributes to tumorigenesis of lung adenocarcinoma in association with the Wnt/β-catenin signaling pathway

Abstract Background Protein regulator of cytokinesis-1 (PRC1) belongs to the microtubule-associated proteins (MAPs) family, and is involved in cytokinesis. Recent investigations suggest PRC1 involvement in human carcinogenesis, including breast carcinoma, hepatocellular carcinoma and etc. However, whether PRC1 contributes to lung adenocarcinoma tumorigenesis remains unknown. Methods Quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blotting and Immunohistochemical staining (IHC) were used to evaluate and contrast the PRC1 expression profile in lung adenocarcinoma and adjacent normal lung tissues. We examined the clinical use of PRC1 in lung adenocarcinoma prognosis. Additionally, the tumorigenesis impact of PRC1 in lung adenocarcinoma cells was verified via in vitro and in vivo metastasis and tumorigenesis assays. Notably, Next Generation Sequencing (NGS) was performed to investigate the molecular mechanism underlying the oncogenic role of PRC1 in lung adenocarcinoma. Results PRC1 mRNA and protein expressions were upregulated in lung adenocarcinoma tissues compared to adjacent normal lung tissues. PRC1 protein overexpression correlated with lymph node metastasis and was an independent poor prognostic factor for lung adenocarcinoma patients. Our data implied that PRC1 depletion limited the proliferation and invasion of lung adenocarcinoma cells in vitro and lowered tumor development and lung metastasis in vivo. Remarkably, limiting PRC1 substantially prompted G2/M phase cell cycle arrest and apoptosis. Mechanistically, by conducting NGS on PRC1-depleted A549 cells and control cells, we discovered that PRC1 expression was significantly correlated with the Wnt signaling pathway. Conclusions This investigation offers confirmation that PRC1 is a prognostic and promising therapeutic biomarker for people with lung adenocarcinoma and takes on a key part in the activation of the Wnt/β-catenin pathway in lung adenocarcinoma development

Additional file 6: Figure S5. of PRC1 contributes to tumorigenesis of lung adenocarcinoma in association with the Wnt/β-catenin signaling pathway

The morphology of A549 cell transduced with shControl and shPRC1. A549 cells transduced with shPRC1–1(B) and shPRC1–2(C) were shrunken and detached compared to the control group (A). (TIFF 7217 kb

Additional file 7: Figure S6. of PRC1 contributes to tumorigenesis of lung adenocarcinoma in association with the Wnt/β-catenin signaling pathway

PRC1 knockdown leads to apoptosis in vitro. Apoptosis in A549 (A) and SPC-A1 (B) cells transduced with shPRC1 was performed by flow cytometry. (TIFF 3598 kb

Additional file 4: Figure S3. of PRC1 contributes to tumorigenesis of lung adenocarcinoma in association with the Wnt/β-catenin signaling pathway

PRC1 knockdown significantly attenuates NSCLC cell migration in vitro. Transwell assays were performed to determine the migratory abilities of A549 (A), SPC-A1 (B), and H1299 (C) cells transduced with lentiviruses expressing the indicated shRNA. (TIFF 21391 kb