International Immunology 2009 21(6):NP; doi:10.1093/intimm/dxp055
© 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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Murine mast cells express CRTH2
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Mast cells are a major source of prostaglandin D
2 (PGD
2). Here,
Boehme et al. (p. 621) show that mouse bone-marrow-derived mast
cells express CRTH2 (chemoattractant receptor homologous molecule
expressed on T
h2 cells) — a PGD
2 receptor. Activation
of mast-cell CRTH2 triggers signalling, modification of cell
surface receptors, and cell migration. The authors suggest a
role for PGD
2–CRTH2 in allergy.
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Gene expression profiles in mouse models of asthma
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Genetic backgrounds affect susceptibility to asthma, and
Dent and colleagues (p. 633) identify several differentially expressed
genes in the lung when comparing three strains of mice that
show varying asthma-like symptoms in response to challenge with
the allergen ovalbumin. In particular, the authors suggest that
eosinophil survivin levels and apoptosis contribute to disease
susceptibility.
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A role for dopamine in Th2 differentiation
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Here,
Matsushita and colleagues (p. 645) show that human monocyte-derived
dendritic cells (DCs) synthesize and store dopamine and release
it during antigen-specific interactions with naïve CD4
+ T cells. The dopamine release induces T
h2 polarisation, whereas
inhibition of release shifts polarisation towards T
h1. DCs are
therefore a novel source of dopamine, which is involved in T
h2
differentiation.
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Irradiated CIITA+ tumour cells in anti-tumour vaccination
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Transfection of mammary carcinoma cells with CIITA (class II
MHC transactivator) leads to strong class II expression.
Accolla and colleagues (p. 655) irradiated such cells for use as a vaccine
against parental tumours in mice. Effective CD4
+ help is generated
for CTLs and nearly all mice are protected. This strategy could
prove useful for cell-based human anti-tumour immunotherapy.
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LPA inhibits NK cell cytotoxicity
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Lysophosphatidic acid (LPA) is a know activator and chemoattractant
for NK cells, and signals via G
i proteins. Using human NK cells,
Norgauer and colleagues (p. 667) show that LPA inhibits cytotoxicity
and perforin release after recognition of tumour cells and can
therefore contribute to escape from immunosurveillance. The
authors also detail the role of G
s-protein signalling in this
phenomenon.
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Geranylgeranylation in Treg and Th17 cell differentiation
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Post-translational protein modifications include addition of
geranylgeranyl groups derived from the cholesterol synthesis
pathway, which statins inhibit.
Nakajima and colleagues (p. 679) show that simvastatin acts similarly to a geranylgeranyl
tranferase inhibitor in inhibiting T
h17 cell differentiation
while enhancing regulatory T (Treg) cell differentiation. The
authors derive a mechanism for statins' anti-inflammatory effects
and a more-general role for geranylgeranylation.
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Nitrilase 1 negatively regulates T cells
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Mammalian nitrilase 1 (Nit1) functions as a tumour suppressor.
In mice with a conditional T-cell Nit1-knockout,
Zhang and colleagues (p. 691) see no obvious effects on T cell numbers or lymphoid
malignancies; however, T cell apoptosis is impaired and T cells
hyperproliferate after TCR stimulation. The authors conclude
that Nit1 is a novel negative regulator in T cells.
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Prediction of HLA-DQ8-binding T cell epitopes
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To identify β-cell epitopes that bind HLA-DQ8 and affect
autoimmune diabetes,
Chang and Unanue (p. 705) adapted a computational
program that then worked better than the others available. In
mice many, but not all, peptides with strong binding-motifs
were immunogenic; but some peptides with weak binding-motifs
were immunogenic. Predictive programs are thus useful, but have
limitations.
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Bim and IL-7 in B cell lymphopoiesis
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Alves and colleagues (p. 715) show for the first time that deficiency
of one Bcl-2-family member (Bim), but not another (Puma), partially
recues B cell development and differentiation in mice lacking
IL-7. The absence of Bim in mice with normal IL-7 levels also
enhances B cell numbers. The authors propose a Bim-dependent,
IL-7-independent mechanism of B cell homeostasis.
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Notch 3 and pre-TCR co-operate in Tregs
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Notch-3-mediated signalling enhances the development and function
of naturally occurring CD4
+CD25
+ regulatory T cells (T
regs).
Here,
Screpanti and colleagues (p. 727) show that pre-TCR
is
required for
in vivo T
reg function and co-operates in many of
the Notch-3-dependent effects on T
regs. In particular, pre-TCR
appears important for Notch-3-mediated protection after triggering
autoimmune diabetes in a mouse model.
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FDC IL-6 mediates optimal B cell responses
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Using IL-6-knockout mice and chimeras of knockout and wild-type
mice,
Tew and colleagues (p. 745) demonstrate for the first
time that immune complexes induce IL-6 production in follicular
dendritic cells (FDCs) and that this FDC-derived IL-6 is crucial
in vivo for optimal germinal centre reactions, and also affects
somatic hypermutation rates and production of specific IgG.
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Murine mast cells express...
Gene expression profiles in...