Airway Basal Cells, Protectors of Epithelial Walls in Health and Respiratory Diseases

Abstract

The airway epithelium provides a critical barrier to the outside environment. When its integrity is impaired, epithelial cells and residing immune cells collaborate to exclude pathogens and to heal tissue damage. Healing is achieved through tissue-specific stem cells: the airway basal cells. Positioned near the basal membrane, airway basal cells sense and respond to changes in tissue health by initiating a pro-inflammatory response and tissue repair via complex crosstalks with nearby fibroblasts and specialized immune cells. In addition, basal cells have the capacity to learn from previous encounters with the environment. Inflammation can indeed imprint a certain memory on basal cells by epigenetic changes so that sensitized tissues may respond differently to future assaults and the epithelium becomes better equipped to respond faster and more robustly to barrier defects. This memory can, however, be lost in diseased states. In this review, we discuss airway basal cells in respiratory diseases, the communication network between airway basal cells and tissue-resident and/or recruited immune cells, and how basal cell adaptation to environmental triggers occurs.

Neuronal-Immune Cell Units in Allergic Inflammation in the Nose

“…[20] "Neurogenic" inflammation [18,21] Neuroendocrine Hypothalamus, pituitary gland, and peripheral endocrine glands (i.e., HPA axis on the whole) Endocrine gland cells NEC [11,22,23] General adaptation syndrome [16] Immune Primary, secondary, and tertiary organs Immune cells (lymphocytes and non-lymphoid immune cells) Immune cell-derived extracellular vesicles [24] Barrier epithelium's cells (ciliated, deuterosomal, goblet, club, basal, suprabasal, tuft cells, ionocytes, etc. [7,10] Innate immunity Pathways of adaptive immune responses Immune (allergen) tolerance [25,26]…”

“…Nowadays, omics technologies [100] such as scRNA-seq, mass spectrometry (MS)based proteomic methods such as matrix-assisted laser desorption/ionization time-offlight MS (MALDI-TOF/TOF-MS) [101] and liquid chromatography tandem MS (LC-MS/MS) [102], and phenotyping could elucidate the heterogeneity of cells and mucus proteins [103] as new biomarkers, neuropeptides, and enzymes critical for neurotransmitter synthesis, which are involved in neuronal-immune cell units at the mucociliaryneuroimmunologically active barrier between inhaled air and unified airway [7][8][9][10][11]. However, research of neuro molecules in allergic rhinitis by proteomic and metabolomic techniques is still in progress.…”

“…The barrier epithelium contributes to regional innate and adaptive immunity, and neuroimmune interaction between cells by which it is formed. Recently, the use of a transcriptomic technology, scRNA-seq, enabled a revisal of the contemporary structure of barrier epithelium and identified new cell lineages present among canonical cell types [7][8][9][10][11]106]. The second type of the nasal epithelium is the olfactory epithelium.…”

“…In addition, apically disposed tight junctions between epitheliocytes control ion and metabolite transport, while the adherens junction along with desmosomes formed by cell adhesion molecules such as cadherins provide the epithelium integrity. Destroyed epithelial integrity facilitates the entry of environmental microbes and allergens to the body [10,105,108]. Undoubtedly, mucociliated epitheliocytes of the barrier epithelium belong to the neuroimmune system as an essential compartment.…”

“…The prevalence of allergic diseases, especially allergic rhinitis, is a challenge and provides a rationale for researchers' interest in this pathology. Single-cell RNA-sequencing (scRNA-seq) has enabled a revisal of the landscape of the nasal mucoliated barrier's cells in the nose in allergic rhinitis [6] and study has commenced of the neuroimmune cross-talk in the unified airway at the modern level [7][8][9][10][11]. Unfortunately, there are still many controversial research results of how single cells and neuro molecules interact in allergic inflammation.…”