Imatinib suppresses the peripheral immune response.

<p>(A–D) Genome wide expression array analysis performed on inguinal lymph node cells harvested from imatinib-treated and control rats on day 10 p.i. (Affymetrix 1.0 ST. 3' arrays; n = 6 arrays/experimental group). (A) Functional annotations differentially regulated between imatinib and PBS-treated rats. Immune cell trafficking was profoundly downregulated in the imatinib group (red pie-chart), as well as numerous immune functions (blue pie-chart). Numbers indicate the amount of molecules differentially expressed in the certain biological function. (B–D) Canonical pathways most significantly affected by imatinib treatment. Leucocyte extravasation was downregulated in the imatinib-treated rats, especially matrix metalloproteinases and CXCR3 (B). The anti-inflammatory interleukine response is also downregulated in the imatinib group in contrast to controls (C). The communication between the innate and adaptive immune response, especially Toll-like receptor (Tlr) signaling is generally downregulated in the imatinib group (D). Statistics are calculated using t-test and calculated <i>P</i> values indicated high significance for each presented molecule <i>P</i><0.00001 = ***). Error bars (not visible), S.E.M. (E) Gene expression profiling in inguinal lymph nodes day 10 p.i. by qPCR. mRNA transcript levels for Th2-cell lineage proliferation: <i>IL4</i> and <i>STAT6</i> are higher in imatinib-treated rats., whereas control rats showed elevated mRNA levels for <i>TLR2</i> and <i>CD4</i> transcripts (n = 8 rats/experimental group, both inguinal lymph nodes/animal). (F) MOG-induced IFNγ Elispot analysis on imatinib-treated and control rat spleenocytes harvested on day 10 p.i. ConA used as a positive control, MBP as an unspecific antigen (n = 4 rats/experimental group). Imatinib-treated rats had significantly lower number of proliferating MOG specific T-cells comparing to the controls. (G–H) MOG re-stimulation assay with spleenocytes harvested from imatinib-treated or control mice on day 7 p.i. (n = 4 mice/experimental group). Levels of Th1/Th2 specific cytokines measured after three days <i>in vitro</i> culturing in the presence of MOG, MBP or ConA. (A–F) Imatinib or PBS oral gavage was performed from day 5 p.i until the end of the experiment. (G–H) Imatinib or PBS oral gavage was performed from day 2 p.i until the end of the experiment Error bars, S.E.M. Statistics were calculated using t-test and <i>P</i> values <0.05 were considered significant (<i>P</i><0.05 = *, <i>P</i><0.01 = **, <i>P</i><0.001 = ***).