The Role of the IL23/IL17 Axis in Bronchiolitis Obliterans Syndrome After Lung Transplantation

Abstract

Bronchiolitis obliterans syndrome (BOS) is the leading cause of death after lung transplantation. Treatment is challenging, as the precise pathophysiology remains unclear.We hypothesize that T H 17 lineage plays a key role in the pathophysiology of BOS by linking T-cell activation to neutrophil influx and chronic inflammation.

Th-17 Alloimmune Responses in Renal Allograft Biopsies From Recipients of Kidney Transplants Using Extended Criteria Donors During Acute T Cell–Mediated Rejection

“…CD4þ Th17 cells can promote acute allograft rejection and vasculopathy in animals models (12). In lung transplant recipients, studies have shown that the IL23/IL17 axis is involved in patients with bronchiolitis obliterans syndrome (BOS) (13,14). In kidney transplantation, IL-17 transcripts are observed in kidney transplant biopsy specimens presented with rejection (15).…”

“…Calcineurin inhibitors, steroids, and other commonly used immunosuppressive drugs have little or no effect on the IL-17 signaling pathway. Surprisingly, studies of lung transplantation have shown that macrolide antibiotics (azithromycin and erythromycin) inhibit the progression of Th17-mediated BOS (13,29). However, it is still not clear whether such a strategy could be a useful additional therapy for TCMR in the recipients of kidneys from elderly donors.…”

Heterogeneity of chronic lung allograft dysfunction: Insights from protein expression in broncho alveolar lavage

“…For BAL, two aliquots of sterile 50 mL saline were instilled in the right middle lobe or lingula. The returned fractions were pooled and processed as previously described (13). Total and differential cell counts are routinely performed in the lab as previously reported (13).…”

“…The returned fractions were pooled and processed as previously described (13). Total and differential cell counts are routinely performed in the lab as previously reported (13). Another fraction was immediately centrifuged at 500g for 10 min at 4° and then stored at -80°C.…”

International practical guidelines on diagnosis, prevention and treatment of bronchiolitis obliterans syndrome

“…Следует развивать современные знания о влия нии клеточного старения трансплантата (ускоренно го старения) на его функцию и риск развития СОБ, а также о роли интерлейкина 17 [150][151][152][153][154][155][156], аутоим мунных механизмов, популяций регуляторных лим фоцитов [157][158][159][160][161][162][163], нейтрофильного ответа и меха низмов, приводящих к фиброзу дыхательных путей при гипотетическом феномене эпителиально мезен химальной трансформации (который пока остается гипотетическим и недостаточно хорошо доказан на моделях животных) [164][165][166][167]. При помощи этой информации возможно разработать новые методы терапии, направленные на предотвращение и лече ние СОБ.…”