Immunity & infection
Interleukin (IL)-7 is constantly expressed and IL-7 serum levels are largely influenced by T-cell mediated consumption. Lymphopenia is so far the only described pathology marked by increased IL-7 serum levels.
We found increased IL-7 serum levels in tuberculosis and cystic fibrosis patients who suffer from repeated pulmonary infections. IL-7 levels normalized during therapy of tuberculosis patients and were associated with worsened lung function of cystic fibrosis patients. These findings indicated a novel role of high IL-7 serum levels in immune pathogenesis of infectious diseases. In tuberculosis patients, lower soluble IL-7 receptor concentrations and impaired IL-7 sensitivity of T cells due to decreased IL-7 receptor expression were found as possible triggers of high IL-7 serum levels. In addition, we identified an SNP (i.e. rs1494558) that was associated with protection against tuberculosis and affected soluble and membrane IL-7 receptor a-chain expression. This SNP was previously described to increase the risk for type-1 diabetes and we confirmed lower soluble IL-7 receptor serum levels of type-1 diabetes patients carrying rs1494558. Notably, higher serum IL-7 levels in rs1494558 carriers were found in type-1 diabetes patients as compared to carriers of a protection associated SNP (i.e. rs6897932), who also had lower soluble IL-7 receptor serum levels. These findings argued against an exclusive role of soluble IL-7 receptor in IL-7 regulation. Combined ectopic expression of IL-7 receptor variants in cell lines confirmed that the type-1 diabetes protective SNP markedly enhanced membrane IL-7 receptor a-chain suggesting that IL-7 serum effects were caused by membrane IL-7 receptor function.