Acupuncture Attenuates Allergic Airway Inflammation via CC10-Mediated Modulation of Lung Dendritic Cells

Background: Acupuncture has emerged as a promising complementary therapy for allergic asthma, but the molecular mechanisms underlying its therapeutic effects remain unclear. This study aimed to investigate whether Clara cell 10-kDa protein (CC10), an airway epithelial immunoregulatory protein, mediates the anti-inflammatory actions of acupuncture through the modulation of pulmonary dendritic cells (DCs). Methods: We conducted a clinical study in patients with allergic asthma who underwent acupuncture at GV14 (Dazhui), BL12 (Fengmen), and BL13 (Feishu) acupoints to evaluate changes in asthma control, leukocyte counts, and serum CC10 levels. Parallelly, a house dust mite (HDM)-induced murine asthma model was used to examine the effects of acupuncture on airway hyperresponsiveness, pulmonary inflammation, T helper type 2 (Th2) cytokine production, and CC10 expression. To confirm the role of CC10, wild-type and CC10-deficient mice were compared, focusing on DC subsets analyzed by flow cytometry. Results: Clinically, acupuncture significantly improved Asthma Control Test (ACT) scores, reduced peripheral leukocyte counts, and elevated serum CC10 concentrations. Consistent with these clinical findings, acupuncture attenuated airway hyperresponsiveness, suppressed eosinophilic infiltration, downregulated Th2 cytokines, and restored pulmonary CC10 expression in HDM-challenged mice. Notably, these protective effects were largely abrogated in CC10-deficient mice, which displayed heightened airway inflammation, mucus hypersecretion, and enhanced Th2 responses. Mechanistic studies revealed that acupuncture reduced pro-inflammatory CD11b+ DCs in a CC10-dependent manner, thereby contributing to airway immune homeostasis. Conclusions: Acupuncture attenuates allergic airway inflammation by upregulating CC10 and subsequently modulating pulmonary DC subsets, specifically CD11b+ DCs. These findings elucidate a novel mechanistic basis for the therapeutic efficacy of acupuncture and underscore CC10 as a viable therapeutic target for the management of allergic asthma. Clinical Trial Registration: NCT01931696, https://clinicaltrials.gov/study/NCT01931696.