{"owner": "ArrayExpress Uploader", "pop_total": 0, "species": "mouse", "factors": [{"GSE12389GSM310323": {}}, {"GSE12389GSM310419": {}}, {"GSE12389GSM310441": {}}, {"GSE12389GSM310442": {}}, {"GSE12389GSM310443": {}}, {"GSE12389GSM310444": {}}, {"GSE12389GSM310445": {}}, {"GSE12389GSM310446": {}}], "id": 5449, "ownerprofile_id": "arrayexpress_sid", "platform": 6, "summary_wrapped": "We demonstrate diverse roles of interferon\u2013gamma (IFN-\u03b3) in the induction and regulation of immune-mediated inflammation using a transfer...", "geo_gse_id": "E-GEOD-12389", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 0, "sample_count": 8, "tags": ["cell", "intermediate", "scid"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_gds_id": "", "slug": "transcription-profiling-of-mouse-interferon-i-depe", "geo_id_plat": "E-GEOD-12389_A-AFFY-45", "name": "Transcription profiling of mouse interferon-I?-dependent regulatory circuits in immune inflammation highlighted in diabetes", "created": "Nov.10, 2014", "summary": "We demonstrate diverse roles of interferon\u2013gamma (IFN-\u03b3) in the induction and regulation of immune-mediated inflammation using a transfer model of autoimmune diabetes. The diabetogenic CD4+BDC2.5 (BDC) T cell clone upon transfer into NOD.scid mice induced destruction of islets of Langerhans leading to diabetes. Administration of a neutralizing antibody to IFN-\u03b3 (H22) resulted in long term protection (LTP) from diabetes, with inflammation but persistence of a significant, albeit decreased numbers of \u03b2-cells. BDC T cells were a mixture of cells expressing high, intermediate and low levels of the T cell receptor. Clonotype-low BDC T cells were required for LTP. Furthermore, islet infiltrating leukocytes in the LTP mice contained Foxp3+CD4 T cells. Islet inflammation in both diabetic and LTP mice was characterized by heavy infiltration of macrophages. Gene expression profiles indicated that macrophages in diabetic mice were M1-type, while LTP mice contained M2-differentiated. The LTP was abolished if mice were treated with either an antibody depleting CD4 T cells, or a neutralizing antibody to CTLA-4, in this case, only at a late stage. Neutralization of IL-10, TGF-\u03b2, GITR or CD25 had no effect. Transfer of only clonotype-high expressing BDC T cells induced diabetes but in contrast, H22 antibodies did not inhibit diabetes. While clonotype high T cells induced diabetes even when IFN-\u03b3 was neutralized, paradoxically, there was reduced inflammation and no diabetes if host myeloid cells lacked IFN-\u03b3 receptor. Hence, using monoclonal CD4 T cells, IFN-\u03b3 can have a wide diversity of roles, depending on the setting of the immune process. Experiment Overall Design: Pancreatic islets were laser-capture microdissected from mice injected with diabetogenic T cells. One cohort of mice also received injections with anti-interfereon gamma monoclonal antibody, which protected those mice from developing diabetes. RNA prepared from islets was amplified and analyzed by Affymetrix GeneChips. Each GeneChip was prepared from RNA pooled from 5 mice at each timepoint. GeneChips were prepared from RNA extracted at different days following injection of T cells. The following days were assayed day 0 (i.e., untreated), day 3 (for diabetic and protected islets), day 4 (diabetic and protected), day 5 (only for protected, as diabetic islets were too edematous to dissect), day 8 (diabetic and protected).", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-12389", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-12389/samples/"}