ncRNAs in Type-2 Immunity

Abstract

Immunological diseases, including asthma, autoimmunity and immunodeficiencies, affect a growing percentage of the population with significant unmet medical needs. As we slowly untangle and better appreciate these complex genetic and environment-influenced diseases, new therapeutically targetable pathways are emerging. Non-coding RNA species, which regulate epigenetic, transcriptional and translational responses are critical regulators of immune cell development, differentiation and effector function, and may represent one such new class of therapeutic targets. In this review we focus on type-2 immune responses, orchestrated by TH2 cell-derived cytokines, IL-4, IL-5 and IL-13, which stimulate a variety of immune and tissue responses- commonly referred to as type-2 immunity. Evolved to protect us from parasitic helminths, type-2 immune responses are observed in individuals with allergic diseases, including Asthma, atopic dermatitis and food allergy. A growing number of studies have identified the involvement of various RNA species, including microRNAs (miRNA) and long non-coding (lncRNA), in type-2 immune responses and in both clinical and pre-clinical disease settings. We highlight these recent findings, identify gaps in our understanding and provide a perspective on how our current understanding can be harnessed for novel treat opportunities to treat type-2 immune-mediated diseases.

Epigenetic alterations in skin homing CD4+CLA+ T cells of atopic dermatitis patients

“…We discovered 16 miRNAs to be differently expressed in CD4 + CLA + T cells from AD patients (Fig. 3 ) , all except for miR-21 previously undescribed in AD 12 . The magnitude of the expression differences between patients and controls was small, but the effect sizes for miRNA variation are unknown.…”

“…DNA methylation differences have also been detected in the epidermis of AD patients 11 . Altered expression of microRNAs has also shown to play a crucial role in type 2 immunity and in promoting pathogenic mechanisms in AD 12 – 15 . However, very few studies have analyzed these epigenetic signatures in purified immune cells from AD patients 3 .…”

LncRNATUG1 Facilitates Th2 Cell Differentiation by Targeting the miR-29c/B7-H3 Axis on Macrophages

“…Recent studies have indicated that lncRNAs have the function of sponging miRNA and play an important role in lung diseases such as chronic obstructive pulmonary disease, cancer, and asthma (19). LncRNAs regulate epigenetic, transcriptional, and translational responses, and are critical regulators of immune cell differentiation, especially for type-2 immune responses (20,21). Previous studies have suggested that lncRNA TUG1 participates in the development of cancers (22,23), hypoxic pulmonary hypertension (24), and Alzheimer's disease (25).…”

Functional Intricacy and Symmetry of Long Non-Coding RNAs in Parasitic Infections

“…For further details on the structural classification of lncRNAs, reviews from Dhanoa et al (2018); Zhang et al (2018), andMarchese et al (2017) are excellent resources. That said, lncRNAs are usually transcribed by the RNA polymerase II (Pol II)-dependent process which involves splicing, capping, and poly-adenylation (Bensaoud et al, 2019;Guidi et al, 2020) similarly to mRNA transcription (Marchese et al, 2017). Also, the transcription of lncRNAs is characteristically marked with sequence of initiation, elongation, and termination.…”