Dysregulated IL-7/IL-7R-CD132 Axis and Intestinal Microsporidiosis in Crohn's Disease

Crohn's disease (CD) is frequently accompanied by T-cell lymphopenia and impaired mucosal immunity, conditions that may predispose to intestinal microsporidiosis by Encephalitozoon cuniculi. This prospective case-control study examined the interplay between IL-7/IL-7 receptor (IL-7R) signaling and anti-E. cuniculi immune responses in 50 CD patients and 50 matched healthy controls. Serum IL-7 and anti-E. cuniculi IgG, IgM, IgA and IgE were quantified by ELISA, while intestinal expression of IL-7, CD127 (IL-7Rα) and CD132 (IL-7Rγ) was assessed by RT-PCR. Protein levels of IL-7 and caspase-3 were evaluated by Western blot, and lymphocyte subsets and apoptosis by flow cytometry. CD patients showed reduced anti-E. cuniculi IgG and IgM levels but increased seropositivity, indicating compromised humoral quality despite greater exposure. Compared with controls, CD was associated with decreased serum IL-7, increased mucosal IL-7, downregulated CD132, and diminished caspase-3, suggesting a disrupted IL-7/IL-7R-apoptosis pathway. In CD, IgA- and IgE-skewed responses correlated differentially with caspase-3 and CD56⁺ γδ T cells, while E. cuniculi seropositivity independently predicted a shorter surgery-free interval. These findings identify a profound dysregulation of the IL-7/IL-7R-CD132-caspase-3 axis in CD and implicate E. cuniculi exposure as a potential marker of impaired mucosal immunity and adverse outcomes.