Wei Cao

The University of Texas Health Science Center at Houston

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Stephanie Dorta‐Estremera

University of Puerto Rico System

Michel Gilliet

University of Lausanne

Yui-Hsi Wang

Cincinnati Children's Hospital Medical Center

TŻ

Tomasz Żal

The University of Texas MD Anderson Cancer Center

Yi-Hong Wang

The University of Texas MD Anderson Cancer Center

Yong‐Jun Liu

South China University of Technology

Jérémy Di Domizio

University of Lausanne

Jens‐Michael Schröder

University Hospital Schleswig-Holstein

Bing Su

Shanghai Jiao Tong University

Michael B. A. Oldstone

Scripps Research Institute

Cooperative Institutions

The University of Texas MD Anderson Cancer Center

The University of Texas Health Science Center at Houston

Scripps Research Institute

University of Iowa

Howard Hughes Medical Institute

Sun Yat-sen University

Melanoma Institute Australia

Peking University

Yale University

Chinese Academy of Sciences

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Topographic Gravity Waves Observed in the Martian Thermosphere: A Statistical Perspective From a 1‐D Full‐Wave Model

Journal of Geophysical Research Space Physics (2022)

Jianping Huang Zhaopeng Wu Jun Cui Yongqiang Hao Wei Cao

Abstract Gravity waves (GWs) are significant dynamical processes in planetary atmospheres due to their efficient transport of momentum and energy from the lower to the upper atmosphere. Recent observations from in‐situ measurements by spacecraft like Mars Atmosphere and Volatile Evolution (MAVEN) also reveal ubiquitous GW activity in the Martian thermosphere. As a critical parameter for characterizing GWs, the wavelength spectrum has been studied for years. However, most of the current observations for the Martian thermosphere can only determine the apparent GW wavelength because they usually take one‐dimensional measurements within a typical GW period. In this work, we adopt a full‐wave GW model to statistically investigate the upward propagation of the topographic‐generated GWs and how their wavelength spectrum apparently looks in the thermosphere when observed by a spacecraft like MAVEN. We find that the wind significantly modifies the vertical wavelengths of GWs in the Martian atmosphere. Considering the GWs generated from topographic sources, we calculate their wavelength distribution in the thermosphere, with a most probable apparent vertical wavelength of around 14 km, consisting with the MAVEN observation. However, our theoretical wavelength spectrum is mainly concentrated in the low wavelength part (10–20 km), while the observed result contains a long‐tailed component in the long wavelength part. The mismatch between our model and observations indicates that at least 72% of the observed GWs in the thermosphere are not generated from topographic sources.

Atmosphere of Mars

10.1029/2022ja030846

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Citations (7)

Methylated BSA Mimics Amyloid-Related Proteins and Triggers Inflammation

PLoS ONE (2013)

Jérémy Di Domizio Stephanie Dorta‐Estremera Wei Cao

The mechanistic study of inflammatory or autoimmune diseases requires the generation of mouse models that reproduce the alterations in immune responses observed in patients. Methylated bovine serum albumin (mBSA) has been widely used to induce antigen-specific inflammation in targeted organs or in combination with single stranded DNA (ssDNA) to generate anti-nucleic acids antibodies in vivo. However, the mechanism by which this modified protein triggers inflammation is poorly understood. By analyzing the biochemical properties of mBSA, we found that mBSA exhibits features of an intermediate of protein misfolding pathway. mBSA readily interact with a list of dyes that have binding specificity towards amyloid fibrils. Intriguingly, mBSA displayed cytotoxic activity and its binding to ssDNA further enhanced formation of beta-sheet rich amyloid fibrils. Moreover, mBSA is recognized by the serum amyloid P, a protein unanimously associated with amyloid plaques in vivo. In macrophages, we observed that mBSA disrupted the lysosomal compartment, signaled along the NLRP3 inflammasome pathway, and activated caspase 1, which led to the production of IL-1β. In vivo, mBSA triggered rapid and prominent immune cell infiltration that is dependent on IL-1β induction. Taken together, these data demonstrate that by mimicking amyloidogenic proteins mBSA exhibits strong innate immune functions and serves as a potent adjuvant. These findings advance our understanding on the underlying mechanism of how aberrant immune responses lead to autoimmune reactions.

Amyloid (mycology)

10.1371/journal.pone.0063214

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Regulation of T-cell activation and migration by the kinase TBK1 during neuroinflammation

Nature Communications (2015)

Jiayi Yu Xiaofei Zhou Mikyoung Chang Mako Nakaya Jae–Hoon Chang

Abstract Development of an immune or autoimmune response involves T-cell activation in lymphoid organs and subsequent migration to peripheral tissues. Here we show that T-cell-specific ablation of the kinase TBK1 promotes T-cell activation but causes retention of effector T cells in the draining lymph node in a neuroinflammatory autoimmunity model, experimental autoimmune encephalomyelitis (EAE). At older ages, the T-cell-conditional TBK1-knockout mice also spontaneously accumulate T cells with activated phenotype. TBK1 controls the activation of AKT and its downstream kinase mTORC1 by a mechanism involving TBK1-stimulated AKT ubiquitination and degradation. The deregulated AKT-mTORC1 signalling in turn contributes to enhanced T-cell activation and impaired effector T-cell egress from draining lymph nodes. Treatment of mice with a small-molecule inhibitor of TBK1 inhibits EAE induction. These results suggest a role for TBK1 in regulating T-cell migration and establish TBK1 as a regulator of the AKT-mTORC1 signalling axis.

TANK-binding kinase 1

10.1038/ncomms7074

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Citations (102)

Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus

Nature (2005)

Norihiko Watanabe Yi-Hong Wang Heung Kyu Lee Tomoki� Ito Yui-Hsi Wang

10.1038/nature03886

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Citations (748)

Identification of α-Dystroglycan as a Receptor for Lymphocytic Choriomeningitis Virus and Lassa Fever Virus

Science (1998)

Wei Cao Michael D. Henry Persephone Borrow Hiroki Yamada John H. Elder

A peripheral membrane protein that is interactive with lymphocytic choriomeningitis virus (LCMV) was purified from cells permissive to infection. Tryptic peptides from this protein were determined to be α-dystroglycan (α-DG). Several strains of LCMV and other arenaviruses, including Lassa fever virus (LFV), Oliveros, and Mobala, bound to purified α-DG protein. Soluble α-DG blocked both LCMV and LFV infection. Cells bearing a null mutation of the gene encoding DG were resistant to LCMV infection, and reconstitution of DG expression in null mutant cells restored susceptibility to LCMV infection. Thus, α-DG is a cellular receptor for both LCMV and LFV.

Lassa virus

Arenavirus

Junin virus

10.1126/science.282.5396.2079

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Citations (678)

Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide

Nature (2007)

Roberto Lande Josh Gregorio Valeria Facchinetti Bithi Chatterjee Yi-Hong Wang

TLR7

Plasmacytoid dendritic cell

Interferon type I

10.1038/nature06116

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Citations (1,790)

Nucleic acid-containing amyloid fibrils potently induce type I interferon and stimulate systemic autoimmunity

Proceedings of the National Academy of Sciences (2012)

Jérémy Di Domizio Stephanie Dorta‐Estremera Mihai Gagea Dipyaman Ganguly Stephan Meller

The immunopathophysiologic development of systemic autoimmunity involves numerous factors through complex mechanisms that are not fully understood. In systemic lupus erythematosus, type I IFN (IFN-I) produced by plasmacytoid dendritic cells (pDCs) critically promotes the autoimmunity through its pleiotropic effects on immune cells. However, the host-derived factors that enable abnormal IFN-I production and initial immune tolerance breakdown are largely unknown. Previously, we found that amyloid precursor proteins form amyloid fibrils in the presence of nucleic acids. Here we report that nucleic acid-containing amyloid fibrils can potently activate pDCs and enable IFN-I production in response to self-DNA, self-RNA, and dead cell debris. pDCs can take up DNA-containing amyloid fibrils, which are retained in the early endosomes to activate TLR9, leading to high IFNα/β production. In mice treated with DNA-containing amyloid fibrils, a rapid IFN response correlated with pDC infiltration and activation. Immunization of nonautoimmune mice with DNA-containing amyloid fibrils induced antinuclear serology against a panel of self-antigens. The mice exhibited positive proteinuria and deposited antibodies in their kidneys. Intriguingly, pDC depletion obstructed IFN-I response and selectively abolished autoantibody generation. Our study reveals an innate immune function of nucleic acid-containing amyloid fibrils and provides a potential link between compromised protein homeostasis and autoimmunity via a pDC-IFN axis.

Amyloid (mycology)

10.1073/pnas.1206923109

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Citations (54)