IL-13+Type 2 Innate Lymphoid Cells Correlate with Asthma Control Status and Treatment Response.
Type 2 innate lymphoid cells (ILC2s) have been shown to produce large amounts of type 2 cytokines in a non-antigen-specific manner. These cytokines act upstream and downstream of ILC2 and are increasingly common in asthma drug development, thus warranting a closer investigation of the mechanism-related clinical manifestations of ILC2 in the selection of patients with asthma. We hypothesized that IL-13+ILC2s in the circulation might correlate with asthma control status as a result of persistent T-helper cell type 2 (Th2) inflammation in the lung. Furthermore, we aimed to explore ILC2s' responsiveness to glucocorticoid. The percentages of ILC2s and IL-13+ILC2s in different asthma subgroups were checked, and correlation analyses between ILC2s and asthma-related clinical parameters were performed. Dexamethasone treatments in ILC2s and Th2 cells were performed to clarify their response properties. ILC2s were identified as a Lin-CD45hiIL-7Rα+CRTH2+cell population distinct from human peripheral blood mononuclear cells. Frequencies of ILC2s were increased dramatically in those with asthma (0.04 ± 0.02%) compared with healthy donors (0.025 ± 0.011%). The percentages of IL-13+ILC2s were significantly higher in patients in the uncontrolled group (49.7 ± 16.9%) and partly controlled groups (30.8 ± 13.1%) than in those in the well-controlled group (16.7 ± 5.9%) and healthy control subjects (18.7 ± 8.7%). Effective treatment of uncontrolled IL-13+ILC2-positive patients with asthma resulted in dynamic modulation of IL-13+ILC2 levels back to baseline. ILC2s were more resistant to glucocorticoid than Th2 cells in vitro. ILC2s are strong responders to IL-25/IL-33 stimulation. IL-13+ILC2s show a positive correlation with patient asthma control status and are more resistant to glucocorticoid than Th2 cells in humans.
1 Asia & Emerging Markets iMed, AstraZeneca Innovative Medicine and Early Development, Shanghai, China; and.
Yi
Y
Jia
1 Asia & Emerging Markets iMed, AstraZeneca Innovative Medicine and Early Development, Shanghai, China; and.
Xu
X
Fang
1 Asia & Emerging Markets iMed, AstraZeneca Innovative Medicine and Early Development, Shanghai, China; and.
Xuehua
X
Zhu
2 Respiratory Division of Zhongshan Hospital, Shanghai Institute of Respiratory Disease, and.
Chunxue
C
Bai
2 Respiratory Division of Zhongshan Hospital, Shanghai Institute of Respiratory Disease, and.
Lei
L
Zhu
2 Respiratory Division of Zhongshan Hospital, Shanghai Institute of Respiratory Disease, and.
Meiling
M
Jin
3 Research Center of Zhongshan Hospital, Fudan University, Shanghai, China.
Xiangdong
X
Wang
1 Asia & Emerging Markets iMed, AstraZeneca Innovative Medicine and Early Development, Shanghai, China; and.
Min
M
Hu
1 Asia & Emerging Markets iMed, AstraZeneca Innovative Medicine and Early Development, Shanghai, China; and.
Renhong
R
Tang
2 Respiratory Division of Zhongshan Hospital, Shanghai Institute of Respiratory Disease, and.
Zhihong
Z
Chen
D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016022:Case-Control Studies; D002452:Cell Count; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D018793:Interleukin-13 / Q000378:metabolism*; D020381:Interleukin-17 / Q000494:pharmacology; D000067596:Interleukin-33 / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018418:Th2 Cells; D014019:Tissue Donors; D016896:Treatment Outcome
D018793:Interleukin-13; D020381:Interleukin-17; D000067596:Interleukin-33; D003907:Dexamethasone
IL-13; ILC2; glucocorticoid; innate immunity; uncontrolled asthma