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Article ; Online: An intranasal influenza virus-vectored vaccine prevents SARS-CoV-2 replication in respiratory tissues of mice and hamsters.

Deng, Shaofeng / Liu, Ying / Tam, Rachel Chun-Yee / Chen, Pin / Zhang, Anna Jinxia / Mok, Bobo Wing-Yee / Long, Teng / Kukic, Anja / Zhou, Runhong / Xu, Haoran / Song, Wenjun / Chan, Jasper Fuk-Woo / To, Kelvin Kai-Wang / Chen, Zhiwei / Yuen, Kwok-Yung / Wang, Pui / Chen, Honglin

Nature communications

2023 Volume 14, Issue 1, Page(s) 2081

Abstract: Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper ... ...

Abstract	Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper respiratory to prevent or reduce infections caused by highly transmissible variants of SARS-CoV-2 are urgently needed. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with a deleted NS1 gene that encodes cell surface expression of the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, designated DelNS1-RBD4N-DAF. Immune responses and protection against virus challenge following intranasal administration of DelNS1-RBD4N-DAF vaccines were analyzed in mice and compared with intramuscular injection of the BioNTech BNT162b2 mRNA vaccine in hamsters. DelNS1-RBD4N-DAF LAIVs induced high levels of neutralizing antibodies against various SARS-CoV-2 variants in mice and hamsters and stimulated robust T cell responses in mice. Notably, vaccination with DelNS1-RBD4N-DAF LAIVs, but not BNT162b2 mRNA, prevented replication of SARS-CoV-2 variants, including Delta and Omicron BA.2, in the respiratory tissues of animals. The DelNS1-RBD4N-DAF LAIV system warrants further evaluation in humans for the control of SARS-CoV-2 transmission and, more significantly, for creating dual function vaccines against both influenza and COVID-19 for use in annual vaccination strategies.
MeSH term(s)	Animals ; Cricetinae ; Humans ; Influenza Vaccines ; SARS-CoV-2/genetics ; Administration, Intranasal ; COVID-19 Vaccines ; COVID-19/prevention & control ; Spike Glycoprotein, Coronavirus/genetics ; Antibodies, Neutralizing ; BNT162 Vaccine ; Orthomyxoviridae ; Antibodies, Viral
Chemical Substances	Influenza Vaccines ; spike protein, SARS-CoV-2 ; COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; Antibodies, Neutralizing ; BNT162 Vaccine ; Antibodies, Viral
Language	English
Publishing date	2023-04-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-37697-1
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Article ; Online: Regulatory T-cells regulate neonatal heart regeneration by potentiating cardiomyocyte proliferation in a paracrine manner.

Li, Jiatao / Yang, Kevin Y / Tam, Rachel Chun Yee / Chan, Vicken W / Lan, Hui Yao / Hori, Shohei / Zhou, Bin / Lui, Kathy O

Theranostics

2019 Volume 9, Issue 15, Page(s) 4324–4341

Abstract: The neonatal mouse heart is capable of transiently regenerating after injury from postnatal day (P) 0-7 and macrophages are found important in this process. However, whether macrophages alone are sufficient to orchestrate this regeneration; what ... ...

Abstract	The neonatal mouse heart is capable of transiently regenerating after injury from postnatal day (P) 0-7 and macrophages are found important in this process. However, whether macrophages alone are sufficient to orchestrate this regeneration; what regulates cardiomyocyte proliferation; why cardiomyocytes do not proliferate after P7; and whether adaptive immune cells such as regulatory T-cells (Treg) influence neonatal heart regeneration have less studied.
MeSH term(s)	Adoptive Transfer ; Aging/physiology ; Animals ; Animals, Newborn ; Cell Proliferation ; Fibrosis ; Forkhead Transcription Factors/metabolism ; Gene Expression Regulation, Developmental ; Heart/physiology ; Humans ; Immunity, Innate ; Loss of Function Mutation/genetics ; Macrophages/metabolism ; Mice, Inbred NOD ; Mice, SCID ; Myocardial Infarction/pathology ; Myocardial Infarction/physiopathology ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism ; Paracrine Communication ; Regeneration/immunology ; T-Lymphocytes, Regulatory/immunology ; Transcriptome/genetics ; Up-Regulation/genetics
Chemical Substances	Forkhead Transcription Factors ; Foxp3 protein, mouse
Language	English
Publishing date	2019-06-09
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592097-2
ISSN	1838-7640 ; 1838-7640
ISSN (online)	1838-7640
ISSN	1838-7640
DOI	10.7150/thno.32734
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Article: A Phase 1, Randomized, Double-Blinded, Placebo-Controlled and Dose-Escalation Study to Evaluate the Safety and Immunogenicity of the Intranasal DelNS1-nCoV-RBD LAIV for COVID-19 in Healthy Adults.

Zhang, Ruiqi / Chan, Kwok-Hung / Wang, Pui / Zhou, Runhong / Yau, Henry Kwong-Chi / Wong, Creany Ka-Wai / Au, Meena Wai-Lam / Tam, Anthony Raymond / Ng, Chi-Tao / Lou, Matthew Kwok-Chung / Liu, Na / Huang, Haode / Deng, Shaofeng / Tam, Rachel Chun-Yee / Liu, Ying / Long, Teng / Tsoi, Hoi-Wah / Ng, Miko K W / Cai, Jian-Piao /

To, Kelvin Kai-Wang / Yuen, Man-Fung / Chen, Zhiwei / Chen, Honglin / Yuen, Kwok-Yung / Hung, Ivan Fan-Ngai

Vaccines

2023 Volume 11, Issue 4

Abstract: An intranasal COVID-19 vaccine, DelNS1-based RBD vaccines composed of H1N1 subtype (DelNS1-nCoV-RBD LAIV) was developed to evaluate the safety and immunogenicity in healthy adults. We conducted a phase 1 randomized, double-blinded, placebo-controlled ... ...

Abstract	An intranasal COVID-19 vaccine, DelNS1-based RBD vaccines composed of H1N1 subtype (DelNS1-nCoV-RBD LAIV) was developed to evaluate the safety and immunogenicity in healthy adults. We conducted a phase 1 randomized, double-blinded, placebo-controlled study on healthy participants, age 18-55 and COVID-19 vaccines naïve, between March and September 2021. Participants were enrolled and randomly assigned (2:2:1) into the low and high dose DelNS1-nCoV-RBD LAIV manufactured in chicken embryonated eggs or placebo groups. The low and high-dose vaccine were composed of 1 × 10
Language	English
Publishing date	2023-03-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11040723
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Article ; Online: MicroRNA-155 Mediates Augmented CD40 Expression in Bone Marrow Derived Plasmacytoid Dendritic Cells in Symptomatic Lupus-Prone NZB/W F1 Mice.

Yan, Sheng / Yim, Lok Yan / Tam, Rachel Chun Yee / Chan, Albert / Lu, Liwei / Lau, Chak Sing / Chan, Vera Sau-Fong

International journal of molecular sciences

2016 Volume 17, Issue 8

Abstract: Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease characterized by hyperactivated immune responses to self-antigens and persistent systemic inflammation. Previously, we reported abnormalities in circulating and bone marrow ( ... ...

Abstract	Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease characterized by hyperactivated immune responses to self-antigens and persistent systemic inflammation. Previously, we reported abnormalities in circulating and bone marrow (BM)-derived plasmacytoid dendritic cells (pDCs) from SLE patients. Here, we aim to seek for potential regulators that mediate functional aberrations of pDCs in SLE. BM-derived pDCs from NZB/W F1 mice before and after the disease onset were compared for toll-like receptor (TLR) induced responses and microRNA profile changes. While pDCs derived from symptomatic mice were phenotypically comparable to pre-symptomatic ones, functionally they exhibited hypersensitivity to TLR7 but not TLR9 stimulation, as represented by the elevated upregulation of CD40, CD86 and MHC class II molecules upon R837 stimulation. Upregulated induction of miR-155 in symptomatic pDCs following TLR7 stimulation was observed. Transfection of miR-155 mimics in pre-symptomatic pDCs induced an augmented expression of Cd40, which is consistent with the increased CD40 expression in symptomatic pDCs. Overall, our results provide evidence for miR-155-mediated regulation in pDC functional abnormalities in SLE. Findings from this study contribute to a better understanding of SLE pathogenesis and ignite future interests in evaluating the molecular regulation in autoimmunity.
MeSH term(s)	Animals ; Antigen Presentation ; Bone Marrow Cells/metabolism ; CD40 Antigens/genetics ; CD40 Antigens/metabolism ; Cells, Cultured ; Dendritic Cells/metabolism ; Female ; Gene Expression ; Lupus Erythematosus, Systemic/metabolism ; Membrane Glycoproteins/metabolism ; Mice, Transgenic ; MicroRNAs/physiology ; RNA Interference ; Toll-Like Receptor 7/metabolism
Chemical Substances	CD40 Antigens ; Membrane Glycoproteins ; MicroRNAs ; Mirn155 microRNA, mouse ; Tlr7 protein, mouse ; Toll-Like Receptor 7
Language	English
Publishing date	2016-08-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms17081282
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Article ; Online: B-cell-targeted therapies in systemic lupus erythematosus.

Chan, Vera Sau-Fong / Tsang, Helen Hoi-Lun / Tam, Rachel Chun-Yee / Lu, Liwei / Lau, Chak-Sing

Cellular & molecular immunology

2013 Volume 10, Issue 2, Page(s) 133–142

Abstract: Autoreactive B cells are one of the key immune cells that have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). In addition to the production of harmful auto-antibodies (auto-Abs), B cells prime autoreactive T cells as antigen- ... ...

Abstract	Autoreactive B cells are one of the key immune cells that have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). In addition to the production of harmful auto-antibodies (auto-Abs), B cells prime autoreactive T cells as antigen-presenting cells and secrete a wide range of pro-inflammatory cytokines that have both autocrine and paracrine effects. Agents that modulate B cells may therefore be of potential therapeutic value. Current strategies include targeting B-cell surface antigens, cytokines that promote B-cell growth and functions, and B- and T-cell interactions. In this article, we review the role of B cells in SLE in animal and human studies, and we examine previous reports that support B-cell modulation as a promising strategy for the treatment of this condition. In addition, we present an update on the clinical trials that have evaluated the therapeutic efficacy and safety of agents that antagonize CD20, CD22 and B-lymphocyte stimulator (BLyS) in human SLE. While the results of many of these studies remain inconclusive, belimumab, a human monoclonal antibody against BLyS, has shown promise and has recently been approved by the US Food and Drug Administration as an indicated therapy for patients with mild to moderate SLE. Undoubtedly, advances in B-cell immunology will continue to lead us to a better understanding of SLE pathogenesis and the development of novel specific therapies that target B cells.
MeSH term(s)	Animals ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/metabolism ; Antigen-Presenting Cells/pathology ; B-Lymphocyte Subsets/immunology ; B-Lymphocyte Subsets/metabolism ; B-Lymphocyte Subsets/pathology ; Cell Death/immunology ; Cytokines/metabolism ; Disease Models, Animal ; Growth Inhibitors/metabolism ; Humans ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/pathology ; Lupus Erythematosus, Systemic/therapy ; Molecular Targeted Therapy/methods
Chemical Substances	Cytokines ; Growth Inhibitors
Language	English
Publishing date	2013-01-28
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2435097-7
ISSN	2042-0226 ; 1672-7681
ISSN (online)	2042-0226
ISSN	1672-7681
DOI	10.1038/cmi.2012.64
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Article ; Online: Low dose inocula of SARS-CoV-2 Alpha variant transmits more efficiently than earlier variants in hamsters.

Mok, Bobo Wing-Yee / Liu, Honglian / Deng, Shaofeng / Liu, Jiayan / Zhang, Anna Jinxia / Lau, Siu-Ying / Liu, Siwen / Tam, Rachel Chun-Yee / Cremin, Conor J / Ng, Timothy Ting-Leung / Leung, Jake Siu-Lun / Lee, Lam-Kwong / Wang, Pui / To, Kelvin Kai-Wang / Chan, Jasper Fuk-Woo / Chan, Kwok-Hung / Yuen, Kwok-Yung / Siu, Gilman Kit-Hang / Chen, Honglin

Communications biology

2021 Volume 4, Issue 1, Page(s) 1102

Abstract: Emerging variants of SARS-CoV-2 have been shown to rapidly replace original circulating strains in humans soon after they emerged. There is a lack of experimental evidence to explain how these natural occurring variants spread more efficiently than ... ...

Abstract	Emerging variants of SARS-CoV-2 have been shown to rapidly replace original circulating strains in humans soon after they emerged. There is a lack of experimental evidence to explain how these natural occurring variants spread more efficiently than existing strains of SARS-CoV-2 in transmission. We found that the Alpha variant (B.1.1.7) increased competitive fitness over earlier parental D614G lineages in in-vitro and in-vivo systems. Using hamster transmission model, we further demonstrated that the Alpha variant is able to replicate and shed more efficiently in the nasal cavity of hamsters than other variants with low dose and short duration of exposure. The capability to initiate effective infection with low inocula may be one of the key factors leading to the rapid transmission of emerging variants of SARS-CoV-2.
MeSH term(s)	Animals ; COVID-19/genetics ; COVID-19/pathology ; COVID-19/transmission ; Cell Line/virology ; Cricetinae ; Disease Models, Animal ; Humans ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; Virus Replication/genetics
Language	English
Publishing date	2021-09-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-021-02640-x
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Article ; Online: Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models.

EBioMedicine

2021 Volume 75, Page(s) 103762

Abstract: Background: Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal.: Methods: Since mucosal immunity is critical for nasal prevention, we investigated the ... ...

Abstract	Background: Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal. Methods: Since mucosal immunity is critical for nasal prevention, we investigated the efficacy of an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2. Findings: Substantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity. Interpretation: Our results demonstrated that intranasal influenza-based boost vaccination induces mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems. Funding: This study was supported by the Research Grants Council Collaborative Research Fund, General Research Fund and Health and Medical Research Fund in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program and matching fund from Shenzhen Immuno Cure BioTech Limited; the Health@InnoHK, Innovation and Technology Commission of Hong Kong; National Program on Key Research Project of China; donations from the Friends of Hope Education Fund; the Theme-Based Research Scheme.
MeSH term(s)	Administration, Intranasal ; Animals ; COVID-19/genetics ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/genetics ; COVID-19 Vaccines/immunology ; Chlorocebus aethiops ; Disease Models, Animal ; Dogs ; Female ; HEK293 Cells ; Humans ; Immunity, Mucosal ; Immunization, Secondary ; Influenza Vaccines/genetics ; Influenza Vaccines/immunology ; Madin Darby Canine Kidney Cells ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Vaccines, Attenuated/genetics ; Vaccines, Attenuated/immunology ; Vaccines, DNA/genetics ; Vaccines, DNA/immunology ; Vero Cells
Chemical Substances	COVID-19 Vaccines ; Influenza Vaccines ; Vaccines, Attenuated ; Vaccines, DNA
Language	English
Publishing date	2021-12-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2021.103762
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Article ; Online: Characterization of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein.

Wang, Pui / Lau, Siu-Ying / Deng, Shaofeng / Chen, Pin / Mok, Bobo Wing-Yee / Zhang, Anna Jinxia / Lee, Andrew Chak-Yiu / Chan, Kwok-Hung / Tam, Rachel Chun-Yee / Xu, Haoran / Zhou, Runhong / Song, Wenjun / Liu, Li / To, Kelvin Kai-Wang / Chan, Jasper Fuk-Woo / Chen, Zhiwei / Yuen, Kwok-Yung / Chen, Honglin

Nature communications

2021 Volume 12, Issue 1, Page(s) 2790

Abstract: SARS-CoV-2 is of zoonotic origin and contains a PRRA polybasic cleavage motif which is considered critical for efficient infection and transmission in humans. We previously reported on a panel of attenuated SARS-CoV-2 variants with deletions at the S1/S2 ...

Abstract	SARS-CoV-2 is of zoonotic origin and contains a PRRA polybasic cleavage motif which is considered critical for efficient infection and transmission in humans. We previously reported on a panel of attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction of the spike protein. Here, we characterize pathogenicity, immunogenicity, and protective ability of a further cell-adapted SARS-CoV-2 variant, Ca-DelMut, in in vitro and in vivo systems. Ca-DelMut replicates more efficiently than wild type or parental virus in Vero E6 cells, but causes no apparent disease in hamsters, despite replicating in respiratory tissues. Unlike wild type virus, Ca-DelMut causes no obvious pathological changes and does not induce elevation of proinflammatory cytokines, but still triggers a strong neutralizing antibody and T cell response in hamsters and mice. Ca-DelMut immunized hamsters challenged with wild type SARS-CoV-2 are fully protected, with little sign of virus replication in the upper or lower respiratory tract, demonstrating sterilizing immunity.
MeSH term(s)	Animals ; COVID-19/diagnosis ; COVID-19/immunology ; COVID-19/virology ; Cell Line, Tumor ; Chlorocebus aethiops ; Cricetinae ; Cytokines/immunology ; Cytokines/metabolism ; Female ; Host-Pathogen Interactions ; Humans ; Male ; Mesocricetus ; Mice, Inbred BALB C ; Mutation ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Spike Glycoprotein, Coronavirus/genetics ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Vero Cells ; Virulence/genetics ; Virulence/immunology ; Virus Replication/genetics ; Mice
Chemical Substances	Cytokines ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-05-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-23166-0
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Article ; Online: Low dose inocula of SARS-CoV-2 B.1.1.7 variant initiate more robust infections in the upper respiratory tract of hamsters than earlier D614G variants

Mok, Bobo Wing-Yee / Liu, Honglian / Lau, Siu-Ying / Deng, Shaofeng Deng / Liu, Siwen / Tam, Rachel Chun-Yee / Ng, Timothy Ting-Leung / Leung, Jake Siu-Lun / Wang, Pui / To, Kelvin Kai-Wang / Chan, Jasper Fuk-Woo / Chan, Kwok-Hung / Yuen, Kwok-Yung / Siu, Gilman Kit-Hang / Chen, Honglin

bioRxiv

Abstract: There is a lack of experimental evidence to explain how the B.1.1.7 variant spreads more quickly than pre-existing variants in humans. We found that B.1.1.7 displays increased competitive fitness over earlier D614G lineages in an in-vitro system. ... ...

Abstract	There is a lack of experimental evidence to explain how the B.1.1.7 variant spreads more quickly than pre-existing variants in humans. We found that B.1.1.7 displays increased competitive fitness over earlier D614G lineages in an in-vitro system. Furthermore, we demonstrated that B.1.1.7 variant is able to replicate and shed more efficiently in the nasal cavity than other variants with lower dose and shorter duration of exposure.
Keywords	covid19
Language	English
Publishing date	2021-04-19
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2021.04.19.440414
Database	COVID19

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Article ; Online: Human CLEC16A regulates autophagy through modulating mTOR activity.

Tam, Rachel Chun Yee / Li, Michelle Wing Man / Gao, Yan Pan / Pang, Yuen Ting / Yan, Sheng / Ge, Wei / Lau, Chak Sing / Chan, Vera Sau Fong

Experimental cell research

2017 Volume 352, Issue 2, Page(s) 304–312

Abstract: CLEC16A is genetically linked with multiple autoimmune disorders but its functional relevance in autoimmunity remains obscure. Recent evidence has signposted the emerging role of autophagy in autoimmune disease development. Here, by ectopic expression ... ...

Abstract	CLEC16A is genetically linked with multiple autoimmune disorders but its functional relevance in autoimmunity remains obscure. Recent evidence has signposted the emerging role of autophagy in autoimmune disease development. Here, by ectopic expression and siRNA silencing, we show that CLEC16A has an inhibitory role in starvation-induced autophagy in human cells. Combining quantitative proteomics and immunoblotting analyses, we found that CLEC16A likely regulates autophagy by activating mTOR pathway. Overexpression of CLEC16A was found to sensitize cells towards the availability of nutrients, resulting in a heightened mTOR activity, which in turn diminished LC3 autophagic activity following nutrient deprivation. CLEC16A deficiency, on the other hand, delayed mTOR activity in response to nutrient sensing, thereby resulted in an augmented autophagic response. CLEC16A was found residing in cytosolic vesicles and the Golgi, and nutrient removal promoted a stronger clustering within the Golgi, where it was possibly in a vantage position to activate mTOR upon nutrient replenishment. These findings suggest that Golgi-associated CLEC16A negatively regulates autophagy via modulation of mTOR activity, and may provide support for a functional link between CLEC16A and autoimmunity.
MeSH term(s)	Autophagy ; Cytoplasmic Vesicles/metabolism ; Golgi Apparatus/metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Lectins, C-Type/genetics ; Lectins, C-Type/metabolism ; Monosaccharide Transport Proteins/genetics ; Monosaccharide Transport Proteins/metabolism ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	CLEC16A protein, human ; Lectins, C-Type ; Monosaccharide Transport Proteins ; TOR Serine-Threonine Kinases (EC 2.7.1.1)
Language	English
Publishing date	2017-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	1493-x
ISSN	1090-2422 ; 0014-4827
ISSN (online)	1090-2422
ISSN	0014-4827
DOI	10.1016/j.yexcr.2017.02.017
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