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Increased synthesis and intestinal expression of IL-39 in patients with inflammatory bowel disease

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Abstract

IL-39 (Interleukin-39) is a heterodimeric cytokine composed of IL-23p19 and EBI3 (Epstein-Barr virus-induced gene 3) subunits. Despite the evidence that correlates the role of IL-39 in regulating inflammation, its expression in the intestinal microenvironment of IBD (inflammatory bowel disease) patients is still unknown. Thus, this work was focused on characterizing relative mRNA (messenger RNA) IL-39 expression and intestinal synthesis in IBD patients. This study includes 37 patients diagnosed with ulcerative colitis (UC), 15 with Chron’s disease (CD), and 22 controls. Gene expression of IL-39 subunits (IL-23p19/EBI3) was measured by RT-PCR (real time polymerase chain reaction). Intestinal synthesis was evaluated by immunohistochemistry and serum levels by ELISA. Statistical analysis was done using Prism GraphPad V6. Relative mRNA IL-39 expression was increased in patients with active UC and active CD compared to the remission UC, remission CD, and control group. High levels of relative mRNA expression of IL-39 (IL-23p19 subunit) were associated with histological activity. IHQ analysis showed increased IL-39 production in mucosa, submucosa, muscular, and serosa layer of patients with active disease. IL-39 serum production was increased in patients with UC. IL-39 gene’s upregulation was found in patients with active IBD and was associated with severe histological activity in UC. This is the first report regarding the role of IL-39 in patients with IBD. The findings suggest that IL-39 might play a role as an inflammatory mediator in active IBD and could be considered a new alternative in treating this condition.

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Data Availability

Data availability will be provided upon request.

Abbreviations

aUC:

Active ulcerative colitis

aCD:

Active Crohn’s disease

BAFF B:

Cell activation factor

cDNA:

Complementary DNA

DAB:

Diaminobenzidine

dNTPs:

Deoxyribonucleotide triphosphate

EBI3:

Epstein-Barr Virus-Induced Gene 3

GADPH:

Glyceraldehyde-3-phosphate dehydrogenase

HRP:

Horseradish peroxidase

IBD:

Inflammatory bowel disease

IL-39:

Interleukin-39

IL-23p19:

Interleukin 23 p19 subunit

LPS:

Lipopolysaccharide

MgCl2 :

Magnesium chloride

mRNA:

Messenger ribonucleic acid

PCR:

Polymerase chain reaction

RT:

Reverse transcription

RT-PCR:

Real-Time Polymerase Chain Reaction

Rcd:

Remission CD

rUC:

Remission ulcerative colitis

SD:

Standard deviation

SEM:

Standard error of the mean

STAT1/STAT3:

Signal transducer and activator of transcription 1–3

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Funding

This work was supported by funds from the Inflammatory Bowel Disease Clinic at the National Institute of Medical Sciences and Nutrition.

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Authors and Affiliations

  1. Inflammatory Bowel Disease Clinic, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, #15, Col. Belisario Domínguez Sección XVI, 14080, Mexico City, CP, Mexico

    Gabriela Fonseca-Camarillo & Jesús K. Yamamoto-Furusho

  2. Department of Immunology, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico, Mexico City

    Gabriela Fonseca-Camarillo

  3. Department of Experimental Surgery, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

    Janette Furuzawa-Carballeda

  4. Department of Endoscopy, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

    Rafael Barreto-Zúñiga

  5. Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

    Braulio Martínez-Benítez

Authors
  1. Gabriela Fonseca-Camarillo
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  2. Janette Furuzawa-Carballeda
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  3. Rafael Barreto-Zúñiga
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  4. Braulio Martínez-Benítez
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  5. Jesús K. Yamamoto-Furusho
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Contributions

GFC participated during the sample processing, performed RT-qPCR analysis for IL-39 transcript level quantification, performed IHQ analysis for protein expression, and data analysis, and prepared the manuscript, critical reviewing, and bibliographic analysis.

JFC participated during IHQ analysis for protein expression, data analysis, prepared the manuscript, critical reviewing, and bibliographic analysis.

BMB and RBZ participate during the sample acquisition.

JKYF provided the research idea and financial resources as well as assessed clinical, endoscopic and histological findings, data analysis, prepared and coordinated the manuscript editing.

Corresponding author

Correspondence to Jesús K. Yamamoto-Furusho.

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Fonseca-Camarillo, G., Furuzawa-Carballeda, J., Barreto-Zúñiga, R. et al. Increased synthesis and intestinal expression of IL-39 in patients with inflammatory bowel disease. Immunol Res 72, 284–292 (2024). https://doi.org/10.1007/s12026-023-09432-x

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  • DOI: https://doi.org/10.1007/s12026-023-09432-x

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