The role of interleukin-17 during acute rejection after lung transplantation

Abstract

Acute rejection (AR) is an important complication that can occur after lung transplantation and constitutes a risk factor for bronchiolitis obliterans syndrome, which is characterised by a neutrophilic airway inflammation. The specific aim of this study was to investigate the role of interleukin (IL)-17, which promotes chemotaxis of neutrophils by inducing IL-8 production, in AR.Cell differentials, mRNA and protein levels were quantified in bronchoalveolar lavages (BALs) taken from patients at 28 and 90 days after lung transplantation. The patient's rejection status was assessed by transbronchial biopsy.An AR was found in nine out of the 26 patients examined, 28 days after transplantation. The number of BAL neutrophils and lymphocytes were increased in these patients. IL-17 mRNA and protein levels in the BAL were increased in patients with AR. Analysis of BAL obtained at day 90 after transplantation, demonstrated that the increase in IL-17 had disappeared, whereas the increase in neutrophils and lymphocytes persisted.These data showed that interleukin-17 is temporarily upregulated in bronchoalveolar lavage during acute rejection. The number of lymphocytes and neutrophils are increased in bronchoalveolar lavage during acute rejection and may persist up to 2 months after acute rejection. These findings suggest that interleukin-17 is important in the pathophysiology of acute lung rejection.

Interleukin-17-producing T-helper cells and related cytokines in human airways exposed to endotoxin

“…Although IL-17 has already been implicated in inflammatory lung disorders of humans [22][23][24][25][26], and IL-17 and/or IL-17 mRNA has been detected locally in these disorders, the presence of IL-17-containing memory Th cells has not previously been demonstrated in association with increased IL-17 production in the human lungs. The phenotype of the IL-17-containing T-cells demonstrated in the present study resembles what has previously been described for Th17 cells [7,10,27] with respect to these cells being CD4 + memory cells.…”

The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

“…In human lung organ transplantation, IL-17 has also been reported as being elevated during acute rejection [93], while rat models have demonstrated that collagen type V-specific lymphocytes can mediate lung allograft rejection and express IL-17 locally at the site of rejection [94]. In cardiac allograft models, antagonism of the IL-17 network (via expression of an IL-17R-immunoglobin fusion protein) can reduce intragraft production of inflammatory cytokines (namely IFN-g) and prolong graft survival [95].…”

A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT

“…13,19,20 IL-17 has important roles in bridging innate and adaptive immunity, and is involved in the host defense against extracellular pathogens, the pathophysiology of autoimmune diseases, and allograft rejection of solid organs. [21][22][23][24][25][26][27][28][29] Moreover, several reports have so far shown that Th17 cells and IL-17 has a significant impact on the development of acute GVHD in mouse models. [30][31][32][33][34][35] Recent reports have shown association of SNPs in the IL-17 gene with autoimmune diseases such as rheumatoid arthritis and ulcerative colitis.…”