International Immunology 2009 21(7):NP; doi:10.1093/intimm/dxp064
© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
IN THIS ISSUE
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Immunopotency of methylated CpG ODN
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Methylation of CpG-containing oligonucleotides (CpG ODN) usually
abrogates their immunostimulatory activity. Here,
Wilson and colleagues (p. 757) show that if methylated CpG ODN are encapsulated
into liposomal nanoparticles, they are as potent as unmethylated
CpG ODN. Both forms signal via Toll-like receptor 9 and the
authors discuss the implications for recognition of the two
forms of CpG ODN.
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Transgenically activated AhR increases T cell IFN- production
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Aryl hydrocarbon receptor (AhR) is a transcription factor for
several genes in the immune system. In mice with a constitutively
active T-cell-specific AhR transgene,
Nohara et al. (p. 769) find enhanced IFN-
responses to ovalbumin; however, antibody
production and T
h2 responses are not affected. The authors discuss
these findings in relation to previous studies that used AhR
ligands.
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NK cells at the onset of clinical tuberculosis
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Here,
De Maria and colleagues (p. 779) describe NK cell markers
in patients with newly diagnosed lung tuberculosis. Several
parameters are impaired: numbers of CD56
brightCD16
+/– cells; expression of NKp30 and NKp46; cytolytic activity; and
IFN-
production. NK cell function is therefore dramatically
perturbed while tuberculosis emerges from latency, which has
clear implications for immune-mediated prevention of overt disease.
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NK cells kill melanoma stem-cell-like cells
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Cancer stem cells (CSCs) may be treatment-resistant and thus
able to drive tumourigenesis and metastasis, although their
phenotypic characteristics are unclear.
Moretta and colleagues (p.793) find that NK cells efficiently kill melanoma cell lines
that have CSC-like characteristics. Various activating NK-receptors
are involved in tumour cell lysis. The authors propose a role
for NK cells in immunotherapy of melanoma.
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PU.1-mediated gene expression in mast cells
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Mast cells normally express low levels of the transcription
factor PU.1. Here,
Nishiyama and colleagues (p. 803) overexpress
PU.1 in mast cells derived in two different ways from precursors.
Expression of CD11b and F4/80 is increased, as is IL-6 production.
The authors can thus characterise both direct and indirect effects
of PU.1 on monocyte-specific or mast-cell-specific gene expression.
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Nasal troponin improves heart function after MI
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Here,
Weiner and colleagues (p. 817) show that nasal administration
of troponin (found in myocardial cells) before or soon after
myocardial infarction (MI) and reperfusion decreases infarction
size and improves cardiac function. They show the cellular immune
response to be mediated by IL-10-secreting CD4
+ T cells. The
authors discuss therapeutic administration with troponin for
patients with MI.
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Foxo3 in B cell development and activation
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Satterthwaite and colleagues (p. 831) examine a wide range of
B cell function and development in Forkhead box o3 (Foxo3)-knockout
mice. Several aspects are affected, including basal immunoglobulin
levels and numbers of both pre-B cells and recirculating B cells.
The authors describe how Foxo3 is controlled and functions distinctly
from other Foxo family members in B cells.
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Human B and T cell functions in humanised mice
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So-called "supra-immunodeficient" mice can be reconstituted
with human haematopoietic stem cells.
Takahashi and colleagues (p. 843) find that B cell development is partially blocked but
that IgG is produced. Thymic selection is functional and T cells
appear phenotypically normal but have impaired proliferation
and IL-2 production. The authors discuss the potential uses
and also limitations of this system.
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Invariant NKT cells in reactive arthritis
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Using a mouse model of reactive arthritis,
Inman and colleagues (p. 859) investigate the role of invariant NKT cells (iNKT cells).
Pretreatment with
-GalCer (an iNKT activator) reduced disease
severity whereas it was more severe in mice with a knockout
of CD1d (which binds
-GalCer).Thus, iNKT cells help prevent
reactive arthritis and modulate the disease.
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TLR-independent inhibition of antigen uptake in DCs
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Here,
Diebold and colleagues (p. 871) show that viral double-stranded
RNA (dsRNA) analogues and RNA homopolymers reduce antigen uptake
in immature dendritic cells (DCs). Importantly, this effect
is independent of Toll-like receptor (TLR)-mediated DC activation,
and independent of the ability of DCs to stimulate T cells.
The route of uptake appears more important than the amount of
antigen.
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Gfi1 suppresses Th17 differentiation
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Yoshimura and colleagues (p. 881) show that growth factor independent
1 transcription repressor (Gfi1) is reduced in T
h17 cells (and
inducible regulatory T cells) but upregulated in T
h1 and T
h2
cells. Gfi1 is repressed by transforming growth factor β
but enhanced by IFN-
or IL-4. The authors conclude that Gfi1
is a novel negative regulator of T
h17 cell differentiation.
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Immunopotency of methylated CpG...
Transgenically activated AhR...