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Eur. J. Immunol. 2009. 39: 2642–2643

Cover image
The cover image is a colour inverted figure taken from Role of DOCK2 and DOCK180 infetal thymus colonization by Lei et al. (pp. 2695–2702). By co-staining sections of frozen
embryos for CD45 and keratin, the authors elegantly show that a combination ofDOCK2 and DOCK180, two closely related CDM family molecules, plays a significant
role in prevascular fetal thymus colonization.

(pp 2925– 2935)

Plasmacytoid DC promote priming of Th17 and EAE
Plasmacytoid DC (pDC) produce large
amounts of type I IFN upon activation
and are implicated in the pathogenesis ofsystemic autoimmune diseases. In thisissue, Isaksson et al. show that pDC are
important for the initiation of the organspecific autoimmune disease EAE. The
presence of pDC during initiation of EAE
promotes clinical signs of the disease,inflammation and demyelination of theCNS. Type I IFN mediate this effect to

IL-17, bone, and fat: A surprising relationship
Osteoporosis affects millions of women
worldwide. The pathogenesis of osteoporosis
is linked to inflammatory cytokines including TNF-a, IL-1 and IL-6. Mice deficient inthese cytokines are protected from bone loss
following ovariectomy (OVX), the standard
model of post-menopausal osteoporosis.
IL-17, the hallmark cytokine of Th17 cells,
cooperates closely with TNF-a, IL-6 and IL-1
to drive inflammation. IL-17 is also directlybone-destructive in the context of rheumatoid arthritis. Accordingly, one would expect
IL-17 to play a similar pro-inflammatory,
bone-destructive role in osteoporosis. In thissome extent, but the interaction between
pDC and Th17 cells appears to be central.
The numbers of autoimmune Th17 cells,
but not Th1 cells, are much higher in thepresence of pDC during priming. Incontrast, pDC deficiency later in the
disease process leads to exacerbated clinical signs of EAE. These observations arerelevant not only for EAE and MS, but alsofor other autoimmune diseases involving
pDC.

(pp 2831– 2839)

issue, Goswami et al. demonstrate that IL-17
receptor-deficient mice (IL-17RA / ) unexpectedly exhibited accelerated bone loss
following OVX, and also became overweight.
Leptin, a cytokine associated with fat
metabolism and satiety, was also increasedin IL-17RA /mice. In vitro, IL-17
suppressed the adipogenesis and leptin
production of 3T3-L1 cells. Combined withrecent reports showing that IL-17 promotes
osteoblastogenesis, these findings suggestthat IL-17 protects bone during estrogen
deficiency, probably by favoring osteoblastogenesis over adipogenesis.

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

www.eji-journal.eu

FORUMEur. J. Immunol. 2009. 39: 2642–2643(pp 2809– 2821)Dengue and the macrophage paradox
Dengue virus is transmitted by mosquitoes
and causes a systemic inflammation withhigh fever that can progress into dengue
hemorrhagic fever or dengue shock
syndrome. In patients and in mousemodels, the virus is most easily detected
in macrophages, which are believed toplay a key role in establishing andspreading dengue infection in the body.
In this issue, Fink et al. show, contrary toInduced Treg: Just what we need in BMT?
Induced human CD41CD251 T cells havebeen shown to express FOXP3, similar to thenaturally occurring regulatory T cells(nTreg). The inhibitory capacity of these
induced cells is, however, under debate. In
this issue, Stroopinsy et al. investigate
functional characteristics of CD41CD25highFOXP31 cells derived from CD25 precursors following allo-stimulation. Intriguingly,
the resultant CD41CD25high population
concurrently exhibited the regulatory
markers FOXP3, CTLA-4, GITR and theinflammatory cytokines IL-2 and IFN-c.
Similarly to nTreg, induced FOXP31IFN-c1
cells were shown, for the first time, to(pp 2840– 2849)

expectations, depleting macrophages in amouse model of infection leads to anincrease in systemic infection. This,
together with the observation that macrophages infiltrate infected lymphoid organs
in large numbers, suggests that macrophages play a dual role in dengue infection – while macrophages are importantfor establishing infection, macrophages
are also critical for virus control.

(pp 2703– 2715)

markedly inhibit alloreactive T-cell expansion. In contrast to nTreg, the induced cells
did not suppress proliferation against a thirdparty stimulator or cytomegalovirus,
suggesting specific suppressive capacity,
targeted against the original stimulus only.
While selective suppressive capacity of
induced FOXP31IFN-c1 cells would allow
prevention of graft-versus-host disease, theirprominent inflammatory cytokine expression would preserve graft-versus-infectionand -tumor responses. Such unique duality
makes these cells ideal for use as posttransplant graft-versus-host disease prophylaxis.

Mesenchymal stem cells: Immunosuppressant orimmunostimulant?
Mesenchymal stem cell (MSC) treatment
is considered an attractive therapeutic
option to dampen inflammation. Th17cells are a new effector CD41 T-celllineage with distinct cytokines profiles
and are thought to be involved in inflammatory and autoimmune diseases. Given
the suppressive effects of MSC on T cells,
it is possible that MSC may also havethe same effect on Th17 cells. On the& 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheimcontrary, in this issue, Guo et al. demonstrate that fetal bone marrow-derived
MSC (FBM-MSC) promote the expansionof Th17 cells in vitro, with IL-6 and IL-1
being two soluble mediators involved inthis process. FBM-MSC also decreases
the percentage of Th1 cells. This study
therefore demonstrates an unanticipatedimmuno-enhancing function of FBM-MSC
on Th17 cells.

www.eji-journal.eu2643