Table 2. Potential ILC2 targets as novel therapies for chronic lung diseases.

Class of target molecule	Drug	Key results	References
Molecules that activate ILC2s
IL-25/IL-25R	Anti-IL-25 and anti-IL-25R	Pre-clinical. Inhibition of inflammation and airway hyperresponsiveness in experimental models of lung inflammation	183–185
IL-33/IL-33R (ST2)	Anti-ST2 antibody GSK3772847 RG6149/AMG282) Anti-IL-33 ANB020	Antibodies that inhibit IL-33 signaling are in clinical development	186
TSLP/TSLPR	anti-TSLP Tezepelumab	Administration reduced lung inflammation and airways bronchoconstriction in mild asthma, and lowered rates of asthma exacerbations in patients with uncontrolled asthma	155, 187
IL-9/IL-9R	Anti-IL-9 and anti-IL-9R MEDI-528	Humanized IL-9 antagonist that inhibits features of asthma in pre-clinical experimental models. No available data in humans	188
Prostaglandin pathway	CRTH2 antagonists OC000459 (Timapiprant) BI 671800 AZD1981 Fevipiprant	Compounds have entered clinical trials. Notably, Fevipiprant treatment of patients on inhaled corticosteroids improved Forced Expiratory Volume and reduced sputum eosinophilia	189–192
	Anti-huCRTH2 antibody	Pre-clinical humanized anti-huCRTH2 antibody causes depletion of CRTH2-expressing cells	193
Leukotriene pathway	Montelukast and Zafirlukast are cysteinyl leukotriene receptor antagonists	ILC2 expression of type-2 cytokines is partially inhibited by Montelukast in vitro	182, 194
Arginase	2(S)-amino-6-boronohexonic acid (ABH) or S-(2-boronoethyl)-L-cysteine (BEC)	Efficacy in pre-clinical experimental asthma models. Arginase inhibitors are in clinical trials as a cancer therapeutics.	195–198
Beta-2 adrenergic receptor	Beta-2 adrenergic receptor agonists	ILC2 express β2AR and inactivating β2AR resulted in lower helminth burden and more ILC2s, eosinophils, and type 2 cytokine production in mice.	135
Transcription factors
GATA3	Antisense DNAzyme molecule (SB010) that cleaves GATA3 mRNA	Administration of SB010 in a small clinical trial resulted in improved lung function and reduced eosinophilia following allergen provocation	199–201
ILC2-derived cytokines
IL-4	Anti-IL-4 receptor alpha (IL-4R) antibody Dupilumab	The anti-IL-4 receptor alpha (IL-4R) antibody (Dupilumab) that inhibits signaling by both IL-4 and IL-13 has proven efficacious in patients with asthma and atopic dermatitis	202, 203
IL-5	Anti-IL-5 antibody Mepolizumab	Has proven beneficial in the treatment of people with uncontrolled severe eosinophilic asthma	204–207
IL-13	Anti-IL-13 antibody Lebrikizumab Tralokinumab	Limited improvements in lung function in periostin-high and eosinophilic patients, but failed to reduce asthma exacerbations	208, 209