MicroRNA-142 regulates gut associated lymphoid tissues and group 3 innate lymphoid cells.

IF 7.9 2区 医学 Q1 IMMUNOLOGY Mucosal Immunology Pub Date : 2024-09-07 DOI:10.1016/j.mucimm.2024.09.001
Luke B Roberts, Joana F Neves, Dave C H Lee, Sara Valpione, Roser Tachó-Piñot, Jane K Howard, Matthew R Hepworth, Graham M Lord
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Abstract

The transcriptomic signatures that shape responses of innate lymphoid cells (ILCs) have been well characterised, however post-transcriptional mechanisms which regulate their development and activity remain poorly understood. We demonstrate that ILC groups of the intestinal lamina propria express mature forms of microRNA-142 (miR-142), an evolutionarily conserved microRNA family with several non-redundant regulatory roles within the immune system. Germline Mir142 deletion alters intestinal ILC compositions, resulting in the absence of T-bet+ populations and significant defects in the cellularity and phenotypes of ILC3 subsets including CCR6+ LTi-like ILC3s. These effects were associated with decreased pathology in an innate-immune cell driven model of colitis. Furthermore, Mir142-/- mice demonstrate defective development of gut-associated lymphoid tissues, including a complete absence of mature Peyer's patches. Conditional deletion of Mir142 in ILC3s (RorcΔMir142) supported cell-intrinsic roles for these microRNAs in establishing or maintaining cellularity and functions of LTi-like ILC3s in intestinal associated tissues. RNAseq analysis revealed several target genes and biological pathways potentially regulated by miR-142 microRNAs in these cells. Finally, lack of Mir142 in ILC3 led to elevated IL-17A production. These data broaden our understanding of immune system roles of miR-142 microRNAs, identifying these molecules as critical post-transcriptional regulators of ILC3s and intestinal mucosal immunity.

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MicroRNA-142 调节肠道相关淋巴组织和第 3 组先天性淋巴细胞。
影响先天性淋巴细胞(ILCs)反应的转录组特征已经得到了很好的描述,但对其发育和活性的转录后调控机制仍然知之甚少。我们证明肠固有层的 ILC 群表达成熟形式的 microRNA-142 (miR-142),miR-142 是一个进化保守的 microRNA 家族,在免疫系统中具有多种非冗余的调控作用。种系Mir142缺失会改变肠道ILC的组成,导致T-bet+群体缺失,ILC3亚群(包括CCR6+ LTi-like的ILC3)的细胞性和表型出现显著缺陷。这些影响与先天性免疫细胞驱动的结肠炎模型中病理变化的减少有关。此外,Mir142-/-小鼠表现出肠道相关淋巴组织发育缺陷,包括完全没有成熟的佩耶氏斑块。在 ILC3s(RorcΔMir142)中有条件地缺失 Mir142 支持这些 microRNA 在肠道相关组织中建立或维持 LTi-like ILC3s 细胞性和功能的细胞内在作用。RNAseq 分析揭示了这些细胞中可能受 miR-142 microRNAs 调控的几个靶基因和生物通路。最后,ILC3 中缺少 Mir142 会导致 IL-17A 生成增加。这些数据拓宽了我们对 miR-142 microRNA 在免疫系统中作用的认识,确定了这些分子是 ILC3 和肠粘膜免疫的关键转录后调控因子。
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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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