¸ñÀû: Th2 cytokines, such as IL-4 or IL-13, are involved in allergic
inflammation, which impacts epithelial cell populations and their
phenotypes. The bronchial mucosa of allergic respiratory patients
also
exhibits significant levels of IL-5 expression. IL-5 regulates
eosinophil stimulation, migration, maturation, and survival by
binding
the alpha chain of its receptor(IL-5R). Therefore IL-5 has been a
therapeutic target for allergy and eosinophilic diseases. IL-5R
has
been known that it is expressed in eosinophils, basophils and
epithelial cells. Our goal was to investigate the expression of
IL-5R
in different types of cells and its characteristics during
allergic
inflammation. ¹æ¹ý:We performed scRNAseq in cultured primary human nasal
epithelial(HNE)
cells and ex vivo nasal epithelium. The transcriptomic features
in
individual epithelial cells were also determined under IL-4
stimulation.
Immunofluorescence(IF) staining was performed with anti-IL-5R,
anti-
acetylated tubulin(ciliated cell marker), anti-MUC5AC(goblet
cell), and
anti-KRT5,13 (basal cell) in human eosinophilic nasal polyp
tissue and
eosinophilic-CRS(ECRS) mouse model. We prepared ECRS mouse models
with
HDM extract, Aspergilus fumigatus, Alternaria alternate, and
protease
from S aureus by intranasal instillation for 3 months. °á°ú:We confirmed that ciliated epithelial cells expressed IL-5R more highly
than other cell types using scRNAseq. When HNE cells fully
differentiated after 2 weeks of air-liquid interface (ALI) culture, IL-
5R mRNA levels were significantly higher than when they were cultured
without ALI. The IL-5R mRNA level was significantly decreased in ALI-
cultured HNE cells after treatment with IL-4 for 7 days. This means that
IL-5R expression decreases when ciliated cells are changed into goblet
cell hyperplasia. Using IF, IL-5R was co-localized in tubulin-positive
ciliated cells, but not in MUC5AC-positive goblet cells in human nasal
tissue and mouse nasal tissue. °á·Ð:As a result, the amount of ciliated or goblet cells in the
epithelium
can affect the expression of IL-5R. The expression of IL-5R is
decreased in epithelial cells when goblet cell hyperplasia is
noted
even in the nasal tissues of patients with ECRS. In spite of
this, IL-
5R expression persists even in ECRS nasal tissues when ciliated
cells
dominate. Therefore, blocking the IL-5R may have a different
therapeutic efficacy depending on its status. |