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Eur. J. Immunol. 2009. 39: 2308–2309

Cover image
This cover is specifically designed to celebrate the 2nd European Congress ofImmunology (www.eci-berlin2009.com), to be held September 13–16, 2009 in Berlin.
The cover consists of a collage of images from Iwanami et al. (pp 2606–2616) with
Berlin’s historic Bradenburg Gate, Brandenburger Tor, in the forefront (image of theBrandenburg Gate r ImageState). Iwanami et al.’s elegant study shows that, inaddition, to defective thymus development, teleosts with mutations in KIAA1440,
TRRAP, and SKIV2L2 also exhibit defective development of multiple organs, thus
identifying previously unknown roles of these genes in organ development.

(pp 2617– 2628)

Modulating innate immunity via CD137 ligand
Reverse signaling through CD137L, amember of the TNF family, has beenshown to modulate cellular immuneresponses. The molecular mechanisms
underlying these effects, however, remainelusive. In this issue, Kim et al. demonstrate that in mouse myeloid cells, crosslinking of CD137L with rCD137-Fc protein
phosphorylates Src family tyrosine
kinase(s). It activates both Akt andmTOR/p70S6 kinase in parallel via

Molecular mechanisms for Treg induction
Cellular therapy using Treg is an appealing option for the prevention of autoimmune diseases. One method of inducing
Treg from effector T cells is through T-cellstimulation in the presence of exogenous
TGF-b1. Given that the extent of Foxp3
expression in Treg correlates with theirregulatory function, increasing Foxp3
levels remains a key goal to enhance
efficacy of cellular therapy in clinical
trials. In this issue, Jana et al. show thatboth Smad3 and Smad2 are required forunidentified pathways. CD137L reverse
signal-mediated mTOR/p70S6 kinase
pathway enhances cell viability, adhesionand M-CSF expression. The Akt pathway,
on the other hand, is responsible forinduction of IL-1b. While TLR signals are
responsible for initial activation of innate
immune cells, reverse signaling throughCD137L may serve as a fine-tuning device
when innate immune cells make physicalcontact with T cells.

(pp 2571– 2583)

TGF-b1-induced Foxp3 expression. Incontrast, T-cell stimulation via the NF-kB
pathway is more complex with evidence
for both a positive effect on Foxp3
expression via IL-2 production, and a
repressive effect through the activationof p50, one of the main NF-kB subunits.
Understanding the differential effects ofthese pathways may facilitate the optimization of Treg-generation for the prevention and treatment of autoimmune
diseases in the future.

& 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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Eur. J. Immunol. 2009. 39: 2308–2309(pp 2470– 2481)

Th1 cells regulate a Th17-mediated severe form of murine
schistosomiasisThe role of Th1 vs. Th17 cells in inflammatory diseases remains a controversial
issue. In murine schistosomiasis, both Th1
and Th17 cells are induced in its severe
form: the hepatic egg-induced granulomatous inflammation. In this issue,
Rutitzky et al. use the T-bet-deficient
mice, which have impaired Th1 immunity,
to study the relative importance of theTh1 and Th17 subsets in murine schitosomiasis. T-bet-deficient mice have exacerbated immunopathology with increased
neutrophil-infiltration and hyperactive

Th17 biased immunity: The link between obesity andinflammatory disease?
The incidence of obesity is increasing worldwide and is becoming a major global causeof morbidity and mortality. Obesity has
been epidemiologically linked to numerous
inflammatory conditions including atherosclerosis, autoimmune disease, asthma,diabetes mellitus, and cancer. The cause ofthis association is unclear. In this issue,
Winer et al. show that obesity favours a proinflammatory
Th17-biased
immuneresponse, providing one plausible mechanism to explain the relationship between(pp 2515– 2524)

DC/CD4+ T cells in the lesions. In theinfected T-bet / mice, the absence ofIFN-g correlates with an increase inIL-23p19, IL-17, IL-22 and TNF-a, and witha decrease in IL-4, IL-5 and IL-10. The study
also shows a decrease in markers foralternatively activated macrophages andTreg. Overall, the findings demonstrate thatTh1 cells regulate Th17 cell-mediatedimmunopathology; however, they do not
exclude a pathogenic role of the Th1 subset
in the absence of Th17 cells.

(pp 2629– 2635)

obesity and inflammatory disease. T cells
from obese, but not lean, mice immunizedwith the CNS protein myelin oligodendrocyte glycoprotein (MOG) show enhanced IL17 secretion resulting in the development ofsevere, early onset, autoimmune demyelination. Obese mice were also more prone todeveloping Th17-mediated colitis. These
results highlight the importance of obesity’s
impact on the immune system and on thedevelopment of chronic inflammatory
disease.

Retinoids set the pace
Retinoids appear to control some ratelimiting events during B-cell development.
Progression of the B-cell lineage isremarkably accelerated when retinoids
are added to adult lymphoid progenitor
cultures. In this issue, Chen et al. demonstrate that there is more complexity to thesystem. In contrast to retinoids’ effect on
adult lymphoid progenitor cultures, retinoids inhibit B lymphopoiesis in fetal
progenitor cultures. Interestingly, the& 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

authors also show that retinoids have aninhibitory effect on adult progenitors
when cells are exposed at high doses orfor prolonged periods. Taken together, thedata suggest that fetal lymphoid progenitors may be exposed to retinoids in the
fetal environment and hence the unexpected response to retinoids observed inculture. More importantly, the results
suggest that endogenous retinoids may
regulate B lymphopoiesis.

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