ISG15 is an interferon (IFN)-α/β-inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. Here, we describe human patients with inherited ISG15 deficiency and mycobacterial, but not viral, diseases. The lack of intracellular ISG15 production and protein ISGylation was not associated with cellular susceptibility to any viruses that we tested, consistent with the lack of viral diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15 secretion by leukocytes-granulocyte, in particular-reduced the production of IFN-γ by lymphocytes, including natural killer cells, probably accounting for the enhanced susceptibility to mycobacterial disease. This experiment of nature shows that human ISGylation is largely redundant for antiviral immunity, but that ISG15 plays an essential role as an IFN-γ-inducing secreted molecule for optimal antimycobacterial immunity

Science , 2012

Direct measurement of local oxygen concentration in
the bone marrow 

Characterization of how the microenvironment, or niche, regulates
stem cell activity is central to understanding stem cell biology and
to developing strategies for the therapeutic manipulation of stem
cells1. Low oxygen tension (hypoxia) is commonly thought to be a
shared niche characteristic in maintaining quiescence in multiple
stem cell types2–4. However, support for the existence of a hypoxic
niche has largely come from indirect evidence such as proteomic
analysis5, expression of Hif-1 (also known as Setd2) and related
genes6, and staining with surrogate hypoxic markers (for example,
pimonidazole)6–8. Here we perform direct in vivo measurements of
local oxygen tension (pO2) in the bone marrow . Using
two-photon phosphorescence lifetime microscopy, we determined
the absolute pO2 of the bone marrow to be quite low (,32mmHg)
despite very high vascular density. We further uncovered heterogeneities

 

Nature MAR, 2014

Write a short summary of one of your published articles here. Include a link to the original story online. This is a great way to establish yourself as an experienced, knowledgeable doctor in your field. You can also include important resources for your patients here.

April 4, 2016

Success of colorectal cancer (CRC) screening is dependent in part on the proportion of uptake by thetargeted population. We aimed in this study to identify factors that were associated with willingness toundergo CRC screening based on the health belief model (HBM).

SJI April 4, 2015

In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils

Mar, 2017

In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils

Mar, 2017

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