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Article

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

by
Carolina Hurtado-Marcos
1,*,
Fernando Izquierdo
1,
Soledad Fenoy
1,
Carmen del Águila
1,
Jaume Pérez-Griera
2,
Salvador Benlloch
3,
Cirilo Amorós
3,
Carlos García Ballesteros
4,
Francisca López Chuliá
4,
Juan Carlos Andreu-Ballester
5 and
Carmen Cuéllar
6,*
1
Universidad CEU San Pablo, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Spain
2
Laboratory Department, University Clinical Hospital, 46010 Valencia, Spain
3
Digestive Departament, Arnau de Vilanova Hospital, 46015 Valencia, Spain
4
Hematology Departament, Arnau de Vilanova Hospital, 46015 Valencia, Spain
5
Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, 46020 Benimaclet, Spain
6
Department of Microbiology and Parasitology, Complutense University of Madrid, 28040 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Pathogens 2026, 15(4), 429; https://doi.org/10.3390/pathogens15040429
Submission received: 13 March 2026 / Revised: 14 April 2026 / Accepted: 15 April 2026 / Published: 16 April 2026
(This article belongs to the Section Parasitic Pathogens)
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Abstract

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.
Keywords: Crohn’s disease; Encephalitozoon cuniculi; CD132; caspase-3; γδ T cells; CD56+ lymphocytes; apoptosis; mucosal immunity; biomarkers; surgical outcomes Crohn’s disease; Encephalitozoon cuniculi; CD132; caspase-3; γδ T cells; CD56+ lymphocytes; apoptosis; mucosal immunity; biomarkers; surgical outcomes
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MDPI and ACS Style

Hurtado-Marcos, C.; Izquierdo, F.; Fenoy, S.; Águila, C.d.; Pérez-Griera, J.; Benlloch, S.; Amorós, C.; Ballesteros, C.G.; Chuliá, F.L.; Andreu-Ballester, J.C.; et al. Dysregulated IL-7/IL-7R-CD132 Axis and Intestinal Microsporidiosis in Crohn’s Disease. Pathogens 2026, 15, 429. https://doi.org/10.3390/pathogens15040429

AMA Style

Hurtado-Marcos C, Izquierdo F, Fenoy S, Águila Cd, Pérez-Griera J, Benlloch S, Amorós C, Ballesteros CG, Chuliá FL, Andreu-Ballester JC, et al. Dysregulated IL-7/IL-7R-CD132 Axis and Intestinal Microsporidiosis in Crohn’s Disease. Pathogens. 2026; 15(4):429. https://doi.org/10.3390/pathogens15040429

Chicago/Turabian Style

Hurtado-Marcos, Carolina, Fernando Izquierdo, Soledad Fenoy, Carmen del Águila, Jaume Pérez-Griera, Salvador Benlloch, Cirilo Amorós, Carlos García Ballesteros, Francisca López Chuliá, Juan Carlos Andreu-Ballester, and et al. 2026. "Dysregulated IL-7/IL-7R-CD132 Axis and Intestinal Microsporidiosis in Crohn’s Disease" Pathogens 15, no. 4: 429. https://doi.org/10.3390/pathogens15040429

APA Style

Hurtado-Marcos, C., Izquierdo, F., Fenoy, S., Águila, C. d., Pérez-Griera, J., Benlloch, S., Amorós, C., Ballesteros, C. G., Chuliá, F. L., Andreu-Ballester, J. C., & Cuéllar, C. (2026). Dysregulated IL-7/IL-7R-CD132 Axis and Intestinal Microsporidiosis in Crohn’s Disease. Pathogens, 15(4), 429. https://doi.org/10.3390/pathogens15040429

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