Since increased IL-17A levels are observed to be localized in the lung compartments (BAL and lymphocytes) in comparison to circulating levels, an inhalable PI3Kδ inhibitor, which is currently utilized for inflammatory airway diseases characterized by IL-17A over-secretion, may be a therapeutic option for active TB disease.
T helper 1 (Th1) cells producing interferon gamma (IFN-γ) and Th17 cells producing interleukin-17 (IL-17) play key roles in host protection against TB, whereas Th2 cells producing IL-4 and regulatory T cells (Tregs) facilitate TB disease progression by inhibiting protective Th1 and Th17 responses.
The expression of IL-17 and IL-10 was significantly increased in active TB patients in comparison to that in latent TB or control groups (IL-17: 16.85±9.68 vs. 7.23±5.19 or 8.21±5.51pg/mL, p<0.05; IL-10: 28.70±11.27 vs. 20.25±8.57 or 13.94±9.00pg/mL, p<0.05).
The present findings deepen our understanding of the role of IL-17 in MDR-TB and highlight the influence of the genetic background of the infecting M. tuberculosis strain on the ex-vivo Th17 response.
Therefore, ectopic lung B cell formation is important for containment of M. tuberculosis, and up-regulation of IL-17 and IL-22 responses may be an important mechanism underlying the protective role B cells in human tuberculosis.
Therefore, increased SOCS3 expression in human tuberculosis may reflect polarization toward IL-17-expressing T cells as well as T-cell exhaustion marked by reduced proliferation.
These findings demonstrate that increased PD-1 expression and decreased pSTAT3 expression reduce IL-23 receptor expression and IL-17 production by CD4(+) T cells of tuberculosis patients.
These findings strongly support the development of a NE-TB vaccine as a novel, safe and effective, first-of-kind IL-17 inducing mucosal vaccine for potential use in humans.
To date, only one study performed in Chinese Han population has found an association between IL-17F sequence variants and susceptibility to tuberculosis, but no relationship has been found with another single nucleotide polymorphism (SNP) in IL-17A gene (rs2275913).