Table 2.

Roles of Epithelial Cells and ILC2s in the Innate Immune Axis of Allergic Rhinitis

Cell Type	Key Role	Key Molecules	Specific Mechanisms and Effects	Reference
Epithelial Cells	Immune Sentinels	TSLP, IL-25, IL-33	Respond to allergens (e.g., house dust mites, fungi, pollen) and tissue damage by releasing "alarmins," initiating a type 2 immune response.	28-30
		IL-33	The house dust mite allergen (Der p1) induces its release in a dose- and time-dependent manner.	31
		IL-25	The protease activity and NADPH oxidase activity of pollen play important roles in its release.	33
		TSLP, IL-25, IL-33	Their expression is significantly upregulated in AR and ECRS patients, and their levels positively correlate with clinical severity (e.g., CT scores and eosinophil counts).	30, 31
		TSLP	Nasal epithelial cells in AR patients have intrinsic dysfunction, with baseline mRNA levels significantly higher than in healthy individuals, indicating a "pre-activated" state.	29
		IL-33	Abnormal activation of the upstream Notch-1 signaling pathway can sustain its high expression.	35
		(Various alarmins)	Reduced expression of endogenous protease inhibitors (EPIs) amplifies allergen-induced alarmin release.	34
ILC2s	First Responders	IL-5, IL-13	Directly and rapidly respond to epithelial-derived IL-25, IL-33, and TSLP via surface receptors (e.g., ST2).	36-38
		(Activation)	The activation mechanism is particularly evident in the nasal tissue of AR patients.	39, 40
		(Activation)	In animal models, activation of ILC2s alone, even in the absence of T/B cells, is sufficient to induce nasal inflammation.	41
		(Metabolism)	Upon activation, ILC2s rapidly adjust their metabolism to support efficient effector functions.	42
		IL-5	Primarily responsible for the recruitment and activation of eosinophils.	37, 41
		IL-13	Leads to epithelial hyperplasia and mucus secretion; a key mediator exacerbating nasal epithelial thickening and eosinophil infiltration.	38, 41, 43