Imatinib does not affect cGVHD severity.

<p>Balb/cJ mice were injected i.v. with 10x10⁶ bone marrow cells and 70x10⁶ splenocytes from B10.D2 donor mice after lethal irradiation at 7 Gy. Mice were then given sterile water (n = 21) or imatinib (n = 21) by gavage at the dose of 150 mg/kg/day (50 mg in the morning and 100 mg in the evening) from day +7 post-transplant to the end of the experiment (day +52). <b>(A)</b> Pooled GVHD scoring of three independent groups of mice given or not imatinib, showing no impact of the treatment on cGVHD scores. (B) Evolution of mice weight loss during the experiment showing slightly lower weight loss for imatinib-treated mice reaching statistical significance on day +52. Results are expressed with mean with SEM. *<i>P</i><0.05</p

Imatinib does not affect T-cell (subset) counts at day +35.

<p>Blood samples were collected to at day +35 post-transplant to assess the impact of the treatment on absolute number of T-cell subpopulations. Imatinib treatment did not affect the counts of T-cell subpopulations. Control: n = 9, imatinib: n = 10, syngeneic: n = 6. *<i>P</i><0.05; **<i>P</i><0.01; ***<i>P</i><0.001. Results are expressed in mean with SEM, Mann-Whitney test.</p

Imatinib increases T-cell proliferation at day +21.

<p>Blood samples were collected at day +21 post-transplant to assess T-cell (subpopulation) proliferation (measured by KI67 expression). The results indicate that the expression of Ki67 by CD4+ T cells, CD8+ T cells and Tregs was higher in imatinib-treated mice (n = 12) than in controls (n = 12), while no difference was observed for the other T-cell subsets. *<i>P</i><0.05; **<i>P</i><0.01. Syngeneic mice: n = 5. Results are expressed in mean with SEM, Mann-Whitney test.</p

Imatinib decreases <i>in vivo</i> proliferation of T-cells.

<p>Balb/cJ mice were lethally irradiated and then injected i.v. with 10x10⁶ bone marrow cells from B10.D2 mice on day 0 and 70x10⁶ CFSE-labelled splenocytes on day +14. Mice were then treated with sterile water (n = 10) or imatinib (n = 12) by oral gavage at the dose of 150 mg/kg/day (50 mg in the morning and 100 mg in the evening) directly after splenocytes injection until sacrifice 5 days later. Proliferation was then assessed among total CD3+ T cells, CD4+ T cells, CD8+ T cells and regulatory T cells (Tregs) from imatinib-treated or control mice in the spleen <b>(A)</b>, blood <b>(C)</b> and lymph nodes <b>(D)</b>. <b>(B)</b> Representative histogram showing CFSE dilution of total CD3⁺ T-cells in the spleen. Results are expressed as median, 25^th and 75^th percentiles of the distribution (boxes) and whiskers extending to 5^th and 95^th percentiles. *<i>P</i><0.05, **<i>P</i><0.01. Mann-Whitney test.</p

Imatinib decreases phosphorylation of PDGF-r and c-Abl.

<p>Skin samples from the upper back of each mice were harvested on day +29 post-transplant and directly fixed in formol 10% before being paraffin-embedded. Skin sections were then stained using anti-phospho-PDGFR and anti-phospho-c-Abl to quantify phosphorylation levels of these receptors in the dermis. Samples were quantified by multiplying the staining intensity (scored 0 to 3) by the extent of stained area (scored 0 to 3). <b>(A-B)</b> Immuno-histological evaluation of the phosphorylation level of c-Abl (control: n = 12, imatinib: n = 12, syngeneic: n = 3). <b>(C-D)</b> immune-histological evaluation of the phosphorylation level of the PDGF-receptor (control: n = 11, imatinib: n = 13, syngeneic: n = 3).*<i>P</i><0.05. Results are expressed in median with interquatile range, Mann-Whitney test.</p

Imatinib does not affect T-cell proliferation at day +35.

<p>Blood samples were collected at day +35 post-transplant to assess T-cell proliferation (measured by KI67 expression). Proliferation of naive CD4+ T cells was significantly higher in imatinib- (n = 10) than in water-treated mice (n = 8). Further, compared to scl-cGVHD mice, syngeneic mice (n = 6) had a lower proliferation of CD8+ T cells but a higher proliferation of naive and central memory CD4+ T cells. *<i>P</i><0.05; **<i>P</i><0.01; ***<i>P</i><0.001. Results are expressed in mean with SEM, Mann-Whitney test.</p

Additional file 1: Figure S1. of Azacytidine mitigates experimental sclerodermic chronic graft-versus-host disease

A): Azacytidine administered every fourth day failed to prevent cGVHD. (B) Decitabine administered every other day ameliorated cGVHD. Figure S2: Impact of Azacytidine on blood counts and immune recovery after syngeneic transplantation. Figure S3: Impact of decitabine on skin, lungs and immune recovery. Figure S4: Azacytidine enhances Treg frequency and functions after syngeneic transplantation. Figure S5: Azacytidine does not induce the generation of CD8+FoxP3+ regulatory T cells after allogeneic or syngeneic transplantation. Figure S6: Azacytidine does not restrict T-cell Vβ (TCR Vβ) repertoire diversity on day +35 and +52. (DOCX 10679 kb

The Nigerian market: fuelling conflict or contributing to peace.

The informality of Nigeria's agricultural produce trade has the potential to promote both cooperation and conflict. The food marketing chains are complex networks extending across the country, and often involve diverse ethnic, religious and social groups. Nonetheless, there is potential for a range of trade-related issues to lead to conflict and for extra-trade tensions related to broader structural issues to spill over and erupt in trade contexts. However, market interactions and trading relationships may also facilitate reconciliation because disputing groups need to work together to secure their individual livelihoods. Moreover, market spaces are important potential mediation spaces precisely because they bring conflict related groups together, especially in boundary regions. Particular individuals - including women traders - may act as crucial "connectors" in this respect, linking diverse ethnic and other interest groups