International Immunology 2009 21(4):NP; doi:10.1093/intimm/dxp036
© 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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Innate immunity in Japan: a historical perspective
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In this article,
Kaisho and Takeda (p. 313) outline the history
of research into innate immunity in Japan. They highlight the
many crucial contributions made by Japanese scientists to the
field, specifically describing phagocytic cells and innate immune
responses in cancer. Finally, they highlight the importance
of research in Japan to the burgeoning topic of Toll-like receptors.
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Innate immunity: an update on TLRs, RLRs and NLRs in pathogen recognition
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Here,
Kawai and Akira (p. 317) provide a state-of-the-art review
on three types of pattern-recognition receptor (PRR): Toll-like
receptors (TLRs), retinoic acid-inducible gene-I-like receptors
(RLRs) and nucleotide-binding oligomerization domain-like receptors
(NLRs). They describe receptor expression and structure, ligand
recognition and signalling pathways, and the formation of inflammasomes.
Finally, they broaden the discussion to the way PRRs shape adaptive
immune responses and autoimmunity.
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Bcl-3 inhibits T cell activation and death
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Marrack and colleagues (p. 339) examine Bcl-3 in adjuvant-induced
T cell responses. Although adjuvants increase Bcl-3 protein
levels in activated T cells, adjuvant-enhanced survival can
occur in the absence of Bcl-3. Interestingly, Bcl-3 also acts
early in T cell responses by enhancing survival of naive T cells
and slowing their rate of activation independently of, for example,
antigen-presenting cells.
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Immunization with DNase II leads to DNase and RNase activity
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Catalytically active antibodies occur in several autoimmune
diseases. After immunizing rabbits with DNase II,
Nevinsky et al. (p. 349) isolated antibody fractions that had RNase and/or
DNase activity. These are the first data demonstrating such
activity in anti-idiotype antibodies to DNase II. The authors
discuss the heterogeneity of catalytic activity following immunization
with various nucleic acids.
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GM-CSF enables DCs to produce retinoic acid
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Dendritic cell (DC) aldehyde dehydrogenase genes (e.g.
Aldh1a2)
are needed for retinoic acid production, which has important
effects on lymphocyte function.
Iwata and colleagues (p. 361) identify specific DC subsets expressing
Aldh1a2 and show that
granulocyte/macrophage colony-stimulating factor (GM-CSF) is
crucial for DC retinoic acid production, in synergy with IL-4,
Toll-like receptor ligands and retinoic acid itself.
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Transplantation tolerance induced by selective Treg expansion
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Sakaguchi and colleagues (p. 379) show that lymphocytes that
reconstitute T-cell-deficient mice must contain natural regulatory
T cells (Tregs) to allow later tolerance to skin grafts following
pre-treatment with donor-specific transfusion (DST) and non-depleting
anti-CD4 antibodies. DST and anti-CD4 inhibit alloantigen-specific
non-Treg effector-cell expansion, but Treg expansion is preserved.
As discussed, anti-CD4, anti-CD54 and rapamycin differentially
affect expansion by different mechanisms.
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MEKK3 is crucial for T cell function and development
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The physiological role of MEKK3 (mitogen-activated kinase kinase
kinase 3) in adaptive immunity is somewhat controversial.
Kurosaki and colleagues (p. 393) report that MEKK3 is needed for TCR-mediated
nuclear factor
B activation and for IL-2-mediated proliferation.
Disruption of MEKK3 leads to reduced numbers of thymocytes and
peripheral T cells. MEKK3 is thus crucial for adaptive immunity
as well as for innate immunity.
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A role for c-Abl in peripheral B cell functions
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The tyrosine kinase c-Abl affects bone marrow B cell development.
Here,
Liberatore and Goff (p. 403) show reduced numbers of peritoneal
B-1 cells and splenic transitional and marginal zone B cells
in c-Abl-deficient mice. The authors also demonstrate clear
roles for c-Abl in signalling after CD19 cross-linking or BCR
engagement, suggesting its importance for peripheral B cell
activation as well as development.
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Natural and pathologic antibodies against topoisomerase I
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Antinuclear autoantibodies to DNA topoisomerase I are frequent
in patients with systemic sclerosis (SSc) and systemic lupus
erythematosus (SLE).
Nemeth and colleagues (p. 415) demonstrate
antibodies in normal people and in patients with rheumatic diseases,
as well as identifying two novel fragments characteristic of
a subset of patients with SLE or diffuse cutaneous SSc.
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LFA-1-independent NK cell anti-fungal activity
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Because LFA-1 plays an essential role in many NK cell functions,
Mody and colleagues (p. 423) examine its role in responses to
the yeast
Cryptococcus neoformans. They find that LFA-1 is not
required for recognition, conjugate formation, perforin release
or target lysis. These results point to fundamental differences
in NK cell anti-fungal responses compared with, for example,
anti-tumour responses.
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Responses to NF-L in multiple sclerosis
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Autoantibodies to neurofilament light protein (NF-L) are associated
with cerebral atrophy in multiple sclerosis (MS).
Amor and colleagues (p. 433) compare T cell responses to NF-L and MOG (myelin oligodendrocyte
glycoprotein) in patients with MS. The authors conclude that
responses to NF-L in MS resemble those in healthy controls and
are part of normal immune repertoire.
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Recirculating T cells express L-selectin cyclically
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Using confocal laser scanning microscopy,
Westermann and colleagues (p. 443) examine T cell L-selectin (CD62L) expression. Unlike
LFA-1 and ICAM-1, L-selectin is downregulated independently
of ligand during transit in secondary lymphoid organs, but not
in non-lymphoid organs; then it is re-expressed. L-selectin
is also downregulated during T cell activation, and the authors
discuss implications for its functional roles.
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Fra-1 regulates LPS-mediated responses
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Fos-related antigen 1 (Fra-1) is a member of the activator protein
1 (AP-1) family of transcription factors. Here,
Takeda and colleagues (p. 457) show that Fra-1 suppresses lipopolysaccharide (LPS)-mediated
stimulation of macrophages and associates with Jun. The authors
discuss the importance of mediators such as Fra-1 in regulation
of immune responses, for example Toll-like receptor (TLR)-mediated
inflammatory cytokine production.
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Stromal cell lymphotoxin βR signalling
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Lymphotoxins (LTs) and tumour necrosis factor are important
for stromal cell maturation.
Katakai and colleagues (p. 467) use a cell line that produces CXCL13 (C–X–C chemokine
ligand 13) after LTβR signalling. Stromal cell LTβR
triggers activation of multiple signalling pathways, including
protein kinase C and both canonical and non-canonical nuclear
factor
B pathways. The results have implications for both tissue
organization and immune responses.
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TRAF2 and TRAF3 are both important for CD40 signalling
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To examine the role of TRAF (TNF receptor associated factor)
proteins in CD40-dependent isotype switching and CSR (class-switch
recombination),
Geha and colleagues (p. 477) generated transgenes
that varied in TRAF binding. After examining a range of functional
readouts, the authors conclude that both TRAF2 and TRAF3 can
independently mediate CSR but both are required for optimal
isotype switching.
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