Spectrum of T‐lymphocyte activities regulating allergic lung inflammation

Abstract

Despite advances in the treatment of asthma, optimization of symptom control remains an unmet need in many patients. These patients, labeled severe asthma, are responsible for a substantial fraction of the disease burden. In these patients research is needed to define the cellular and molecular pathways contributing to disease which in large part are refractory to corticosteroid treatment. The causes of steroid-resistant asthma are multifactorial and result from complex interactions of genetics, environmental factors, and innate and adaptive immunity. Adaptive immunity, addressed here, integrates the activities of distinct T cell subsets and by definition is dynamic and responsive to an ever-changing environment and the influences of epigenetic modifications. These T-cell subsets exhibit different susceptibilities to the actions of corticosteroids and, in some, corticosteroids enhance their functional activation. Moreover, these subsets are not fixed in lineage differentiation but can undergo transcriptional reprogramming in a bidirectional manner between protective and pathogenic effector states. Together, these factors contribute to asthma heterogeneity between patients but also in the same patient at different stages of their disease. Only by carefully defining mechanistic pathways, delineating their sensitivity to corticosteroids, and determining the balance between regulatory and effector pathways, will precision medicine become a reality with selective and effective application of targeted therapies.

Acupoint application inhibits nerve growth factor and attenuates allergic inflammation in allergic rhinitis model rats

“…The cytokines secreted by TH2 cells can promote the production of IgE (by B cells). IgE binds to high affinity receptor Fc receptor (Fc epsilon RI) (appeared in mast cells and basophilic granulocyte surface) [25], which promotes the degranulation of mast cells [26], and induces not only the release of histamine, leukotriene and other bioactive mediators, but a variety of pathological reactions (such as increased secretion of smooth muscle contraction and glandular mucus, dilatation of capillaries and small vessels, and increased permeability of blood vessels), leading to the occurrence of AR [27]. From the behavioral point of view, the symptoms of AR rats are consistent with the pathological reaction.…”

Antigen-specific regulatory T-cell responses against aeroantigens and their role in allergy

“…Thus, loss of tolerance requires uptake of the allergen by antigenpresenting cells (APCs) and activation and formation of allergenspecific Th2 cells as the initial event underlying allergy development. 5,7,8 However, even in highly atopic donors, allergy only develops against a limited number of "allergenic proteins" and typically only after several years of exposure, while against the majority of proteins constituting inhaled particles, tolerance is maintained. This highlights that tolerance against aeroantigens is a highly efficient process for most proteins, and that evasion from this tolerance mechanism by allergenic proteins is actually a rather rare event even in susceptible donors.…”

“…The molecular mechanisms for induction of Th2 responses and their downstream effector functions are not part of this review but have been extensively reviewed elsewhere. 5,7,8 The main questions we address are: 1. Which antigen-specific tolerance mechanisms against inhaled antigens are described?…”

Extracellular vesicles and asthma: A review of the literature

“…In chronic cases, persistent changes in airway structure, including sub‐basement fibrosis, mucus hypersecretion, injury to epithelial cells, smooth muscle hypertrophy and angiogenesis, may occur. Interaction between diverse types of cells through mediators often results in airway inflammation and obstruction, as summarized in Figure …”

“…Interaction between diverse types of cells through mediators often results in airway inflammation and obstruction, as summarized in Figure 1. [5][6][7][8] Extracellular vesicles (EVs) are a universal feature of cellular function and can be detected in culture supernatants of different bodily fluids such as serum, bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NLF). 9 Due to these characteristics, there has been an increased interest in EVs and their potential applications in understanding the underlying mechanisms of various lung diseases, their use as biomarkers and therapeutic tools in lung inflammation.…”