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MicroRNA-mediated post-transcriptional regulation of peripheral γδ T cell effector functions
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| Poster | 1.81 MB | Adobe PDF | ||
| Abstract (p. 67) | 1.44 MB | Adobe PDF |
Orientador(es)
Resumo(s)
γδ T cells are unconventional lymphocytes able to rapidly produce large quantities of interleukin-17A (IL-17A) or interferon-γ (IFNγ), which often have major effects on the pathophysiology of diseases such as cancer or infections. Yet, we do not fully understand how the thymic-derived effector γδ T cell subsets making either IL-17A (γδ17 cells) or IFNγ (γδIFN cells) are activated and function in peripheral tissues. Here, we established an Il17a-GFP:Ifng-YFP double-reporter mouse strain to analyse at unprecedented depth the microRNA (miRNA) transcriptomes of pure γδ17 versus γδIFN cell populations from peripheral lymph nodes, and uncover new mechanisms of miRNA-mediated post-transcriptional regulation of γδ T cell effector functions. We found 103 differentially expressed miRNAs between γδ17 and γδIFN cells, from which we selected 10 candidates likely to target members of the transcriptional networks underlying IL-17A of IFN-γ production, to test their effects on γδ T cell differentiation or effector functions. Retroviral gain-of-function approaches in vitro highlighted a plethora of context-dependent miRNA-specific effects on the differentiation or expansion of γδ17 or γδIFN cells, and respective cytokine production. Furthermore, a detailed analysis of each candidate miRNA expression throughout ontogeny showed that in some cases it was imprinted in the thymus, whereas in others it was peripherally induced. This led to the observation that miR-181a-5p, highly expressed in early thymic γδ T cell subsets, favours thymic γδ17 cell commitment, while conversely promoting peripheral γδIFN activation and proliferation in response to TCR stimulation in vitro and upon malaria infection in vivo. On the contrary, we found miR-128-3p to act as a peripheral regulator of IFN-γ, preventing aberrant IFN-γ production upon TCR stimulation. These findings unravel a new layer of regulation of γδ T cell effector functions, which we are further characterizing with additional molecular assays.
Descrição
Palavras-chave
microRNA γδ T cell
Contexto Educativo
Citação
Inácio D, Amado T, Sobral D, Enguita F, Cunha C, Gomes AQ, et al. MicroRNA-mediated post-transcriptional regulation of peripheral γδ T cell effector functions. In: 11th International gdT Cell Conference, Hilton Downtown Toronto (Canada), May 20-23, 2025.