Ex Vivo Overactivation of Lymphocyte Subsets in Fibrotic Hypersensitivity Pneumonitis Is Blunted by a Sphingosine-1-Phosphate Receptor Ligand
Abstract
1. Introduction
2. Results
2.1. Subject’s Characteristics
2.2. Increased Circulating Factors in fHP Patients
2.3. Indications That Specific Lymphocyte Subsets Are Primed and/or Activated in fHP Patients
2.4. Ozanimod Inhibits CD8 T Cell Activation Ex Vivo
2.5. Ozanimod Perturbs B Cell Activation in Response to a TLR9 Ligand
3. Discussion
4. Materials and Methods
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Control Subjects (10) | Patients with fHP (12) | |
---|---|---|
General characteristics | ||
Age (Year ± SEM) | 65.3 ± 2.8 | 67.1 ± 7.1 |
Sex (Male, n *) | 6 | 7 |
Smoker | 0 | 0 |
Non-smoker | 8 | 6 |
Former smoker | 2 | 6 |
fHP treatment at time of blood sampling | N/D | |
Mycophenolate and corticosteroids | 5 | |
Corticosteroids | 1 | |
Without fHP treatment | 6 | |
Clinical data for diagnosis | ||
Environmental exposure confirmed | N/D | 6 |
HRCT ** | N/D | |
Typical fHP | 9 | |
Compatible for fHP | 1 | |
Indeterminate for fHP | 2 | |
Lymphocytosis | N/D | |
Mild (10–20%) | 1 | |
Moderate (20–40%) | 5 | |
Important (>40%) | 3 | |
Biopsy ** | N/D | 10 |
Definite fHP | 6 | |
Probable fHP | 4 | |
Diagnosis confidence ** (Multidisciplinary team meeting) | N/D | |
Definite fHP | 8 | |
High Confidence fHP | 3 | |
Low Confidence fHP | 1 |
Cytokine | Control (pg/mL) (n = 10) | fHP (pg/mL) (n = 9) | p-Value |
---|---|---|---|
TNF | 0.0 (0.0–1.2) | 10.7 (0.4–53.3) | 0.020 * |
CXCL13 | 0.9 (0.0–19.5) | 59.7 (15.1–125.5 | 0.028 * |
BAFF | 469.3 (419.5–564.5) | 593.7 (492.7–937.0) | 0.035 * |
IL-4 | 0.0 (0.0–0.6) | 1.7 (0.1–11.9) | 0.039 * |
IL-21 | 0.0 (0.0–4.8) | 29.3 (0.0–101.3) | 0.050 * |
IL-17A | 0.0 (0.0–1.3) | 1.7 (0.0–74.5) | 0.089 |
IL-6 | 0.0 (0.0–7.6) | 2.7 (0.0–33.4) | 0.154 |
IL-22 | 110.0 (84.7–180.2) | 212.2 (95.9–331.4) | 0.278 |
CXCL12 | 99.9 (85.8–111.2) | 105.7 (63.43–122.4) | 0.720 |
IFNγ | 1.0 (0.0–2.1) | 1.2 (0.0–4.7) | 0.923 |
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Courtemanche, O.; Huppé, C.-A.; Blais-Lecours, P.; Maranda, C.; Morissette, M.C.; Blanchet, M.-R.; Dion, G.; Marsolais, D. Ex Vivo Overactivation of Lymphocyte Subsets in Fibrotic Hypersensitivity Pneumonitis Is Blunted by a Sphingosine-1-Phosphate Receptor Ligand. Int. J. Mol. Sci. 2025, 26, 3197. https://doi.org/10.3390/ijms26073197
Courtemanche O, Huppé C-A, Blais-Lecours P, Maranda C, Morissette MC, Blanchet M-R, Dion G, Marsolais D. Ex Vivo Overactivation of Lymphocyte Subsets in Fibrotic Hypersensitivity Pneumonitis Is Blunted by a Sphingosine-1-Phosphate Receptor Ligand. International Journal of Molecular Sciences. 2025; 26(7):3197. https://doi.org/10.3390/ijms26073197
Chicago/Turabian StyleCourtemanche, Olivier, Carole-Ann Huppé, Pascale Blais-Lecours, Cloé Maranda, Mathieu C. Morissette, Marie-Renée Blanchet, Geneviève Dion, and David Marsolais. 2025. "Ex Vivo Overactivation of Lymphocyte Subsets in Fibrotic Hypersensitivity Pneumonitis Is Blunted by a Sphingosine-1-Phosphate Receptor Ligand" International Journal of Molecular Sciences 26, no. 7: 3197. https://doi.org/10.3390/ijms26073197
APA StyleCourtemanche, O., Huppé, C.-A., Blais-Lecours, P., Maranda, C., Morissette, M. C., Blanchet, M.-R., Dion, G., & Marsolais, D. (2025). Ex Vivo Overactivation of Lymphocyte Subsets in Fibrotic Hypersensitivity Pneumonitis Is Blunted by a Sphingosine-1-Phosphate Receptor Ligand. International Journal of Molecular Sciences, 26(7), 3197. https://doi.org/10.3390/ijms26073197