Genomics

Dataset Information

0

Specific targeting of the common gamma chain blocks cooperative reprogramming of human tissue-resident cytotoxic T lymphocytes by IL-15 and IL-21


ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE120904 | GEO | 2018/10/06

REPOSITORIES: GEO

Similar Datasets

2019-07-26 | GSE134900 | GEO
2012-11-01 | GSE40350 | GEO
| E-GEOD-40350 | biostudies-arrayexpress
| E-GEOD-64713 | biostudies-arrayexpress
2019-02-01 | GSE125983 | GEO
2015-06-16 | GSE64713 | GEO
2008-02-19 | GSE8685 | GEO
2021-05-10 | PXD025891 | Pride
2004-12-11 | GSE2059 | GEO
| E-GEOD-8685 | biostudies-arrayexpress