Using neutron-scattering techniques, we have investigated the nuclear and the magnetic structures of the triangular antiferromagnet 3R-AgNiO 2 . The symmetry analysis based on the group theory suggests that the ͱ 3 ϫ ͱ 3 charge order proposed for 2H-AgNiO 2 ͓E. Wawrzyńska et al., Phys. Rev. Lett. 99, 157204 ͑2007͔͒will have a monoclinic symmetry if present in the trigonal lattice of 3R-AgNiO 2 . The Rietveld refinement shows that symmetry reduction in the NiO 2 layer is consistent with the prediction of the group theory. The pair density function consistently shows that the nearest-neighbor Ni-O bonds split into two groups separated by approximately 0.1 Å. The antiferromagnetic Bragg peaks observed below T N = 25 K can be described by the propagation vector k = ͑0,1,0͒ of the monoclinic unit cell. The similarities of the local structure and the antiferromagnetic order strongly suggest that the novel charge order observed in 2H-AgNiO 2 also exists in 3R-AgNiO 2 .

Background: Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSC) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods: To compare the therapeutic effects between the naïve MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9. Results: Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 up-regulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions: The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.

Human chronic graft-versus-host disease (CGVHD) shares clinical characteristics with a murine sclerodermatous GVHD (scl GVHD) model that is characterized by skin and lung fibrosis. We used B10.D2 → BALB/c model of scl GVHD, which differ at minor histocompatibility loci, to address the therapeutic effect of mesenchymal stem cells (MSCs) on the development of CGVHD. MSCs were intravenously treated on days 3, 5 and 7 post-transplantation. The clinical severity of cutaneous scl GVHD was significantly attenuated after the treatment of MSCs. Pathologically, animals treated with MSCs showed less fibrosis and inflammatory cell infiltrations in skin and ear but not in visceral organs including lung and liver. Accordingly, the mRNA expression of collagen type 1 α1, 1 α2 and 3 α1 as well as collagen production were significantly reduced after the MSC treatment only in skin compared to the allogeneic scl GVHD controls. MSCs down-regulated mRNA of proinflammatory cytokines mainly in skin tissues and among them TGF-β expression was consistently reduced 28 days after HSCT. The effects of MSCs on molecular markers implicated in persistent TGF-β signaling and fibrosis, such as phosphatase and tensin homolog (PTEN), p-Smad2/3 and matrix metaloprotease-1 (MMP-1) were observed at the skin tissues. MSCs inhibited infiltration of immune cells into skin through down-regulating CCR4, CCR8 and CCR10 on donor CD4 T cells and CCR1 on CD11b monocytes. Moreover, MSCs diminished the expression of mRNA for chemokines such as CCL1, CCL8, CCL17, CCL22 and CCL3, in skin. In conclusion, treatment of MSCs early after transplant attenuated cutaneous scl GVHD by selectively blocking of immune cell migration and down-regulating the chemokines and chemokine receptors.

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine caused by chronic and excessive inflammation. Mesenchymal stem cells (MSCs) are pluripotent cells with immunosuppressive properties, currently studied as a potential treatment for IBD. We previously demonstrated that among various TLR ligands, MSCs treated with poly(I:C), which is a TLR3 ligand, more profoundly induced IDO, which is a therapeutically relevant immunosuppressive factor, without any observable phenotype change in vitro. The goal of the study was to determine whether poly(I:C) can enhance the therapeutic efficacy of bone marrow-derived MSCs for the treatment of IBD. To compare the therapeutic effects between naïve MSCs and primed MSCs by poly(I:C) stimulation on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index (DAI) score and body weight loss were significantly improved in the primed MSCs treated mice group. Also the pathologic severity of colon were more recovered in primed MSCs treated group. The frequency of T cells in spleen and mesenteric lymph node was markedly decreased in primed MSCs treated group. Foxp3 expressing regulatory T cells were more expanded in primed MSCs treated group. Treatment of primed MSCs reduced the expression of proinflammatory cytokines in colon tissue. In conclusion, we demonstrate that primed MSCs with poly(I:C) improve their efficacy in treating DSS-induced colitis, and this effect at least partly depends on the enhancement of their immunosuppressive activity through increasing their production of IDO.