ncRNA-regulated immune response and its role in inflammatory lung diseases

Abstract

Despite the greatly expanded knowledge on the regulation of immune response by protein molecules, there is increasing understanding that noncoding RNAs (ncRNAs) are also an integral component of this regulatory network. Abnormal immune response serves a central role in the initiation, progression, and exacerbation of inflammatory lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, and acute respiratory distress syndrome/acute lung injury. Dysregulation of ncRNAs has been linked to various immunopathologies. In this review, we highlighted the role of ncRNAs in the regulation of innate and adaptive immunity and summarized recent findings that ncRNAs participate in the pathogenesis of inflammatory lung diseases via their regulation of pulmonary immunity. We also discussed therapeutic potentials for targeting ncRNAs to treat these lung disorders.

Keywords: acute respiratory distress syndrome; asthma; chronic obstructive pulmonary disease; cystic fibrosis; immunity; noncoding ribonucleic acid.

Fig. 1.

Noncoding RNAs (ncRNAs) play pivotal roles in the differentiation, activation, and function of immunological cells. Dysregulation of specific ncRNAs leads to unsynchroniced immune response that can cause tissue immunopathologies, such as several lung diseases that are characteristic of aberrant immune response. AHR, airway hyperresponsiveness; miRs, micro RNAs; VEGF, vascular endothelial growth factor; DCs, dendritic cells; Th, T helper; lncRNAs, long noncoding RNAs; CFTR, cystic fibrosis transmembrane conductance regulator; TOM1, target of Myb 1; SHIP1, phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1; IRF1, interferon regulatory factor-1; CAV1, caveolin 1; CTSS, cathepsin S; COPD, chronic obstructive pulmonary disease; AAT, α₁-antitrypsin; GRP76, 76-kDa glucose-regulated protein; ATF6, activating transcription factor 6; COX-2, cyclooxygenase-2; PGE₂, prostaglandin E₂; Tregs, T regulator cells; ALI, acute lung injury; Akt, v-akt murine thymoma viral oncogene homolog; C/EBP, CCAAT/enhancer-binding protein; IL, interleukin.