Metabolic Plasticity in Dendritic Cell Responses: Implications in Allergic Asthma

Table 2

Immunological effects of targeting important metabolic signaling pathways in asthma^∗.

Metabolic sensors/target	Asthma model	Examples of agents/treatments	Asthma phenotype	References
mTOR	OVA-induced	mTORC inhibitor rapamycin derivative (SAR 943)	(↓) airway inflammation, Th2 cytokine production, mucous cell metaplasia, and AHR; (↓) CD4^+ T cell numbers, however, failed to decrease AHR and eosinophilia	Fujitani et al. [90]; Eynott et al. [107]
mTOR	Induction and treatment-model of HDM-mediated asthma	mTORC inhibitor; Rapamycin	Airway inflammation, Th2 cytokine production, mucous cell metaplasia, and AHR (↓) in induction model, however, exacerbated AHR and airway inflammation when rapamycin administered later in a treatment model	Fredriksson et al. [88]; Mushaben et al. [89]
Rheb1	OVA-induced	Myeloid-specific Rheb1 deletion	(↑) eosinophilic airway inflammation, mucous production, and AHR	Kai et al. [108]
AMPK	Obese asthma model: high fat-fed diet + OVA	AMPK activator metformin	(↓) BAL eosinophil counts and iNOS expression in lung	Calixto et al. [91]
AMPK/PPAR-γ	OVA-induced	SRT1720; synthetic SRT 1 activator	(↓) BAL eosinophil counts and type 2 cytokine productions	Ichikawa et al. [109]
PPAR-γ	FITC-OVA	PPAR-γ agonist rosiglitazone	Inhibits the migration of DCs from airway mucosa to draining lymph nodes and decrease priming of T cells	Angeli et al. [95]
PPAR-γ	OVA-pulsed DCs	PPAR-γ agonist rosiglitazone	(↓) BAL eosinophil counts and OVA-specific T cell proliferation; (↑) interleukin 10 (IL10) production by T cells	Hammad et al. [96]
PPAR-γ	Obese asthmatics model of a two-center, 12-week randomized double-blinded trial	PPAR-γ agonist pioglitazone	No significant difference in asthma control and treatment group in lung function, (↑) body weight by pioglitazone treatment	Dixon et al. [94]

^∗Note that this list is not exhaustive. Rheb: Ras homolog enriched in the brain (small GTPase downstream target of tuberous sclerosis complex (TSC) 1/2 and upstream activator of mTORC1); OVA: ovalbumin; HDM: house dust mite; mTORC 1: mammalian target of rapamycin complex I; AMPK: AMP-activated protein kinase; PPAR-α: peroxisome proliferator-activated receptor-α; BAL: bronchoalveolar lavage; AHR: airway hyperresponsiveness; iNOS: inducible nitric oxide synthase.