Select conditions below to toggle them from the plot:
GROUP | CONDITION | SAMPLES |
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Intestinal epithelial cells |
GSM3418205 GSM3418212 GSM3418219 GSM3418226 GSM3418233
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GSM3418210 GSM3418217 GSM3418224 GSM3418231 GSM3418238
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GSM3418211 GSM3418218 GSM3418225 GSM3418232 GSM3418239
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GSM3418207 GSM3418214 GSM3418221 GSM3418228 GSM3418235
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GSM3418206 GSM3418213 GSM3418220 GSM3418227 GSM3418234
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GSM3418208 GSM3418215 GSM3418222 GSM3418229 GSM3418236
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GSM3418209 GSM3418216 GSM3418223 GSM3418230 GSM3418237
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Intestinal intraepithelial cytotoxic T cells |
GSM3418240 GSM3418250 GSM3418260 GSM3418270
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GSM3418247 GSM3418257 GSM3418267 GSM3418277 GSM3418281 GSM3418285 GSM3418289
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GSM3418242 GSM3418252 GSM3418262 GSM3418272
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GSM3418249 GSM3418259 GSM3418269 GSM3418279 GSM3418283 GSM3418287 GSM3418291
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GSM3418243 GSM3418253 GSM3418263 GSM3418273
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GSM3418241 GSM3418251 GSM3418261 GSM3418271
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GSM3418245 GSM3418255 GSM3418265 GSM3418275
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GSM3418244 GSM3418254 GSM3418264 GSM3418274
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GSM3418246 GSM3418256 GSM3418266 GSM3418276 GSM3418280 GSM3418284 GSM3418288
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GSM3418248 GSM3418258 GSM3418268 GSM3418278 GSM3418282 GSM3418286 GSM3418290
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Submission Date: Oct 05, 2018
Summary: The common gamma chain (γc) is required for productive signaling by interleukin (IL)-15, IL-21 and IL-2, which are critically involved in immune activation and regulation. IL-21 and IL-15 are implicated in the pathogenesis of type-1 diabetes, graft-versus-host disease, and celiac disease (CeD), a gluten-mediated autoimmune-like enteropathy. Attempts to treat type-1 diabetes and graft-versus-host disease with biologics targeting one particular cytokine have failed. Both IL-15 and IL-21 have been suggested to drive activation of cytotoxic T cells (CTL) that are the effectors mediating tissue destruction in CeD and organ-specific autoimmune disorders. We show that the concomitant upregulation of IL-15 and IL-21 occurs only in full-blown CeD with villous atrophy. BNZ-2, a peptide that targets the γc, was able to block the cooperative IL-15/IL-21 mediated transcriptional activation of human tissue-resident intraepithelial CTL. Importantly, this inhibition was specific and did not interfere with IL-2 signaling, a cytokine with known immunoregulatory functions. Moreover, BNZ-2 blocked gluten-induced IFN-γ production in small intestinal organ cultures from CeD patients. These observations identify BNZ-2 as a therapeutic candidate for immune disorders in which IL-15 and IL-21 cooperate to induce CTL-mediated tissue damage.
GEO Accession ID: GSE120904
PMID: 31622625
Submission Date: Oct 05, 2018
Summary: The common gamma chain (γc) is required for productive signaling by interleukin (IL)-15, IL-21 and IL-2, which are critically involved in immune activation and regulation. IL-21 and IL-15 are implicated in the pathogenesis of type-1 diabetes, graft-versus-host disease, and celiac disease (CeD), a gluten-mediated autoimmune-like enteropathy. Attempts to treat type-1 diabetes and graft-versus-host disease with biologics targeting one particular cytokine have failed. Both IL-15 and IL-21 have been suggested to drive activation of cytotoxic T cells (CTL) that are the effectors mediating tissue destruction in CeD and organ-specific autoimmune disorders. We show that the concomitant upregulation of IL-15 and IL-21 occurs only in full-blown CeD with villous atrophy. BNZ-2, a peptide that targets the γc, was able to block the cooperative IL-15/IL-21 mediated transcriptional activation of human tissue-resident intraepithelial CTL. Importantly, this inhibition was specific and did not interfere with IL-2 signaling, a cytokine with known immunoregulatory functions. Moreover, BNZ-2 blocked gluten-induced IFN-γ production in small intestinal organ cultures from CeD patients. These observations identify BNZ-2 as a therapeutic candidate for immune disorders in which IL-15 and IL-21 cooperate to induce CTL-mediated tissue damage.
GEO Accession ID: GSE120904
PMID: 31622625
Signatures:
Control Condition
Perturbation Condition
Only conditions with at least 1 replicate are available to select
This pipeline enables you to analyze and visualize your bulk RNA sequencing datasets with an array of downstream analysis and visualization tools. The pipeline includes: PCA analysis, Clustergrammer interactive heatmap, library size analysis, differential gene expression analysis, enrichment analysis, and L1000 small molecule search.