Pediatric cystic fibrosis is associated with type 3 immune response

Cystic fibrosis (CF) is an autosomal recessive disorder caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR dysfunction impairs epithelial chloride and bicarbonate transport, leading to dehydrated airway surfaces, mucus accumulation, defective mucociliary clearance, and chronic inflammation. Type 3 immune responses, particularly those involving IL-17 A and IL-22, have been implicated in CF airway disease; however, systemic alterations in these pathways remain incompletely defined, especially in pediatric patients.

Peripheral blood samples were obtained from healthy controls (n = 20), pediatric patients with clinically stable CF (n = 20), and pediatric patients with CF experiencing pulmonary exacerbation (n = 8). Peripheral blood mononuclear cells were isolated by Ficoll-Hypaque density-gradient centrifugation. Following stimulation with phorbol 12-myristate 13-acetate and ionomycin, intracellular IL-17 A, IL-22, and IL-10 production was assessed by flow cytometry in CD3-positive and CD3-negative lymphocyte populations. Plasma IL-17 A, IL-22, and granulocyte-macrophage colony-stimulating factor levels were measured by enzyme-linked immunosorbent assay.

The percentage of lymphocytes was higher in patients with stable CF than in healthy controls and patients experiencing pulmonary exacerbation, whereas absolute lymphocyte numbers were comparable among groups. The absolute number of CD3⁺IL-22⁺ cells was increased in patients with stable CF compared with healthy controls. Both the frequency and absolute number of CD3⁻IL-22⁺ cells were increased in patients with stable CF, while the frequency of CD3⁻IL-22⁺ cells was also increased during pulmonary exacerbation. Plasma IL-17 A concentrations were lower in patients with stable CF than in healthy controls. In addition, the absolute number of CD3⁺IL-10⁺ cells was increased in patients with stable CF. No statistically significant differences were detected in plasma IL-22 or granulocyte-macrophage colony-stimulating factor concentrations.

Pediatric CF is associated with selective alterations in circulating type 3 and regulatory immune responses, characterized by increased IL-22-producing lymphocyte populations, reduced plasma IL-17 A concentrations, and increased numbers of CD3⁺IL-10⁺ cells. These findings suggest that systemic immune regulation in CF differs between stable disease and pulmonary exacerbation and warrant confirmation in larger longitudinal cohorts.