Allergic Asthma Clinical Trial
Official title:
Non-coding RNAs Analysis of Eosinophil Subtypes in Asthma
Chronic airway inflammation rich in eosinophils is an important feature seen in asthma.
Airway and blood eosinophilia is associated with increased rates of asthma exacerbations and
more intense treatment.
Recently, the existence of two distinct eosinophils subtypes was revealed-lung-resident
eosinophils (rEOS), which maturate independently to interleukin (IL) 5, with the primary
function to maintain tissue homeostasis, and inflammatory eosinophils (iEOS), which mature in
IL-5-dependent manner and are mainly involved in immune responses. Eosinophils' effect on the
airway remodeling in asthma depends not only on the activity but also by their viable number
in the lungs. Blood iEOS infiltrate the airways mainly after the environmental stimulus like
allergen and leave the airways with bronchial secretions. However, rEOS reside lung tissue
for their entire lifetime regulating local immunity. Blood rEOS and iEOS ratio alters in
asthma, compared with healthy controls. It is known that the predominant eosinophils subtype
in allergic asthma are iEOS, while rEOS are basic subtype in severe eosinophilic asthma
patients, moreover, they are different in adhesive properties and survivability as well.
Distinct biological properties allows to speculate about their different functions in asthma,
however, there are still little information. Data about differently expressed microRNA
(miRNA) profiles in eosinophils in asthma suggests, that eosinophils subtypes can be distinct
in non-coding RNA (ncRNA) - microRNA (miRNA), piwi-interacting RNA (piRNA) and long
non-coding RNA (IncRNA) profiles that could describe their role in asthma pathogenesis and
act as biomarkers to discern asthma phenotypes.
Asthma is not cured, and only well-balanced treatment can control the course and severity of
the disease. Most clinical symptoms rise from aberrant chronic airway inflammation mostly
eosinophilic. Eosinophils are terminally differentiated granulocytes that actively contribute
to innate and adaptive inflammatory cascades through the production and release of diverse
chemokines, cytokines, lipid mediators and other growth factors. IL-5 plays a fundamental
role in eosinophils maturation in the bone marrow, their recruitment, and activation at sites
of inflammation.
Historically eosinophils were described as a critical player in host defense, including
parasites, viruses, fungi, or bacteria, giving them a destructive inflammatory cell label.
However, it became clear that steady-state eosinophils can contribute to the immunoregulation
and tissue homeostasis as well. Studies revealed that there are distinct eosinophils subtypes
- immunoregulatory lung-resident eosinophils (rEOS) and inflammatory eosinophils (iEOS),
involved in immune responses. Distinct eosinophils subtypes with different functions
determines the separate treatment. There are still only a few studies describing distinct
eosinophils subtypes in the lungs or blood. It is the beginning of a new promising research
area for better individualized eosinophilic asthma treatment, moreover, other eosinophilic
diseases as well.
Peripheral blood eosinophils studies are sufficiently relevant to the tissue eosinophils
studies, as blood eosinophils are released into the bloodstream in a fully maturated form.
Moreover, peripheral blood study could give additional information with possibilities to
prevent eosinophils effects in the early stage, before migration to the airways. Furthermore,
the existence of tissue-resident eosinophils in peripheral blood is confirmed and primary
research for eosinophil subtypes surface markers was made according to the data of human
blood eosinophils.
Data about differently differently expressed microRNA (miRNA) profiles in eosinophils in
asthma suggests, that eosinophils subtypes can be distinct in non-coding RNA (ncRNA) -
microRNA (miRNA), piwi-interacting RNA (piRNA) and long non-coding RNA (IncRNA) profiles that
could describe their role in asthma pathogenesis and act as biomarkers to discern asthma
phenotypes.
Researchers have plan to expand research by analyzing non-coding RNA (ncRNA) - miRNA, piRNA
and lncRNA profiles of rEOS and iEOS as well as selected ncRNA signatures in blood plasma
estimating their diagnostic value. Moreover, additional investigation of ncRNA in
eosinophil-derived exosomes will provide important data about possible effect of eosinophils
subtypes on airway remodeling via secreted ncRNA. ncRNAs are key regulators for gene
transcription. However, there is evidence about their dysregulation in eosinophils during
asthma. It will give important information about molecular signaling pathways that regulate
the activity of distinct eosinophil subtypes during health and asthma, and provide the
essential information about possible new therapeutic targets for their control. Additionally
researchers will investigate the biological differences between rEOS and iEOS, including
surface integrins and eosinophilopoietins receptors expression, adhesive properties,
survivability, synthesized reactive oxygen species and apoptosis, as well as their effect on
pulmonary structural cells physiological activity as proliferation, apoptosis, migration,
contractility and proteins production, and will relate it with molecular signaling pathways,
regulated by distinct expressed ncRNAs. ncRNAs can be stored in eosinophils exosomes and
expressed to the surrounding environment. Information about ncRNAs in eosinophils-derived
exosomes will demonstrate their function by affecting the other cells, especially after
migration to airways. Moreover, ncRNAs are stable and resistant to blood RNases and
differentially expressed in several pathologies. Researchers suppose that altered blood
levels of ncRNAs could act as a possible new diagnostic biomarker in asthma.
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