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Allogeneic T cell responses are regulated by a specific miRNA-mRNA network.

ABSTRACT: Donor T cells that respond to host alloantigens following allogeneic bone marrow transplantation (BMT) induce graft-versus-host (GVH) responses, but their molecular landscape is not well understood. MicroRNAs (miRNAs) regulate gene (mRNA) expression and fine-tune the molecular responses of T cells. We stimulated naive T cells with either allogeneic or nonspecific stimuli and used argonaute cross-linked immunoprecipitation (CLIP) with subsequent ChIP microarray analyses to profile miR responses and their direct mRNA targets. We identified a unique expression pattern of miRs and mRNAs following the allostimulation of T cells and a high correlation between the expression of the identified miRs and a reduction of their mRNA targets. miRs and mRNAs that were predicted to be differentially regulated in allogeneic T cells compared with nonspecifically stimulated T cells were validated in vitro. These analyses identified wings apart-like homolog (Wapal) and synaptojanin 1 (Synj1) as potential regulators of allogeneic T cell responses. The expression of these molecular targets in vivo was confirmed in MHC-mismatched experimental BMT. Targeted silencing of either Wapal or Synj1 prevented the development of GVH response, confirming a role for these regulators in allogeneic T cell responses. Thus, this genome-wide analysis of miRNA-mRNA interactions identifies previously unrecognized molecular regulators of T cell responses.

SUBMITTER: Sun Y

PROVIDER: S-EPMC3809794 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Allogeneic T cell responses are regulated by a specific miRNA-mRNA network.

Sun Yaping Y Tawara Isao I Zhao Meng M Qin Zhaohui S ZS Toubai Tomomi T Mathewson Nathan N Tamaki Hiroya H Nieves Evelyn E Chinnaiyan Arul M AM Reddy Pavan P

The Journal of clinical investigation 20131101 11

Donor T cells that respond to host alloantigens following allogeneic bone marrow transplantation (BMT) induce graft-versus-host (GVH) responses, but their molecular landscape is not well understood. MicroRNAs (miRNAs) regulate gene (mRNA) expression and fine-tune the molecular responses of T cells. We stimulated naive T cells with either allogeneic or nonspecific stimuli and used argonaute cross-linked immunoprecipitation (CLIP) with subsequent ChIP microarray analyses to profile miR responses a ...[more]

PMID: 24216511

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Allogeneic T cell responses are regulated by a specific miRNA-mRNA network.

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Allogeneic T cell responses are regulated by a specific miRNA-mRNA network.

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