Dopamine inhibits group 2 innate lymphoid cell-driven allergic lung inflammation by dampening mitochondrial activity

The role of hormones in ILC2‐driven allergic airway inflammation

“…First, as ILC2s exhibit different phenotypes and functions in different tissue niches, 120 whether hormones affect ILC2 phenotype transformation remains to be determined. Second, the expression of hormone receptors may differ in ILC2s and non‐ILC2 cells 108,110,113 . Whether hormones could mediate different biological effects by acting on different immune cells in allergic airway inflammation is unclear.…”

“…Second, the expression of hormone receptors may differ in ILC2s and non-ILC2 cells. 108,110,113 Whether hormones could mediate different biological effects by acting on different immune cells in allergic airway inflammation is unclear. In particular, ILC2s are regarded as innate counterparts of Th2 cells and their crosstalk may differ in different conditions.…”

“…treating Parkinson's disease, bipolar disorder and [105][106][107] Dopamine receptors (DR) are members of the GPCR superfamily, consisting of DR1-DR5 and dopamine can inhibit ILC2 response. 108 Specifically, clearance of pulmonary dopaminergic neurons with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridi ne by intranasal drops significantly promotes ILC2 activation and exacerbates airway inflammation in mice, whereas intranasal dopamine therapy dramatically attenuates ILC2-mediated allergic lung inflammation. 108 Dopamine effectively inhibits ILC2 proliferation and type 2 cytokine secretion by reducing mitochondrial oxidative phosphorylation (OXPHOS) and ATP production, whereas this effect is almost eliminated in DR1-KO mice.…”

“…108 Dopamine effectively inhibits ILC2 proliferation and type 2 cytokine secretion by reducing mitochondrial oxidative phosphorylation (OXPHOS) and ATP production, whereas this effect is almost eliminated in DR1-KO mice. 108 However, another group showed that the dopamine-DR4 axis enhanced Th2 cell differentiation and function and facilitated the formation of Th2-resident memory cells, thus exacerbating early-life allergic inflammation. 109 In addition, they did not observe DR1-DR5 expression on ILCs and dopamine had no significant impact on ILC2s.…”

“…Dopamine, a widely recognized neurotransmitter and also a hormone, plays a crucial role in regulating various physiological processes and has been employed in treating Parkinson's disease, bipolar disorder and shock 105–107 . Dopamine receptors (DR) are members of the GPCR superfamily, consisting of DR1‐DR5 and dopamine can inhibit ILC2 response 108 . Specifically, clearance of pulmonary dopaminergic neurons with the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine by intranasal drops significantly promotes ILC2 activation and exacerbates airway inflammation in mice, whereas intranasal dopamine therapy dramatically attenuates ILC2‐mediated allergic lung inflammation 108 .…”