T Lymphocytes, Multi-Omic Interactions and Bronchopulmonary Dysplasia

Abstract

Bronchopulmonary dysplasia (BPD) remains a significant clinical challenge in neonatal medicine. BPD is clearly a multifactorial disease with numerous antenatal and postnatal components influencing lung development. Extremely immature infants are born in the late canalicular or early saccular stage and usually receive intensive care until the early alveolar stage of lung development, resulting in varying magnitudes of impairment of alveolar septation, lung fibrosis, and abnormal vascular development. The interactions between T lymphocytes, the genome and the epigenome, the microbiome and the metabolome, as well as nutrition and therapeutic interventions such as the exposure to oxygen, volutrauma, antibiotics, corticosteroids, caffeine and omeprazole, play an important role in pathogenesis and disease progression. While our general understanding of these interactions thanks to basic research is improving, this knowledge is yet to be translated into comprehensive prevention and clinical management strategies for the benefit of preterm infants developing BPD and later during infancy and childhood suffering from the disease itself and its sequelae. In this review, we summarise existing evidence on the interplay between T lymphocytes, lung multi-omics and currently used therapeutic interventions in BPD, and highlight avenues for potential future immunology related research in the field.

CD8A is a Promising Biomarker Associated with Immunocytes Infiltration in Hyperoxia-Induced Bronchopulmonary Dysplasia

“…It has been demonstrated that T lymphocytes plays a crucial role in the pathogenesis and progression of chronic lung disorder in babies born prematurely. 38 Emerging studies have suggested the CD8+ T cells may contribute to the immunopathology in BPD and may increase the risk of respiratory morbidity. 39 Furthermore, the high neutrophil-to-lymphocyte ratio is an early predictor of severe BPD and also a biomarker for the preterm infants with intrauterine infections.…”

Implication of m6A Methylation Regulators in the Immune Microenvironment of Bronchopulmonary Dysplasia

“…In addition, reduced expression of CD14 + CD64 + cells weas observed at 38-40 weeks after conception [32]. The proportion of B cells and CD4 cells (CD62L) was reduced in BPD infants [33].The activation and polarization of macrophages play a crucial role in the development of lung diseases. Increased expression of macrophage-related plasma cytokines was observed in BPD patients.…”

Multiomic Investigations into Lung Health and Disease

“…In a mouse model of BPD, a study of lung microbiome and metabolome in 1–14 days old mice in response to exposure to hyperoxia and lipopolysaccharide (LPS) revealed that hyperoxia increased Intestinimonas abundance, whereas LPS decreased Clostridiales, Dorea, and Intestinimonas; further integration with a published lung transcriptomics signature of hyperoxia derived a gene signature with biomarkers potential for risk of BPD development [ 142 ]. The importance and relevance of lung T-cell multi-omic interactions with the genome, epigenome and microbiome have been reviewed in the context of BPD in preterm infants ( Figure 4 ) [ 143 ].…”