Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P13232 (
Interleukin-7
)
580
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
T-cell proliferation and generation of protective memory during chronic infections depend on
Interleukin-7
(
IL-7
) availability and receptivity. Regulation of
IL-7
receptor (IL-7R) expression and signalling are key for
IL-7
-modulated T-cell functions. Aberrant expression of soluble (s) and membrane-associated (m) IL-7R molecules is associated with development of autoimmunity and immune failure in acquired immune deficiency syndrome (AIDS) patients. Here we investigated the role of
IL-7
/IL-7R on T-cell immunity in human tuberculosis. We performed two independent case-control studies comparing tuberculosis patients and healthy contacts. This was combined with follow-up examinations for a subgroup of tuberculosis patients under therapy and recovery. Blood plasma and T cells were characterised for
IL-7
/sIL-7R and mIL-7R expression, respectively.
IL-7
-dependent T-cell functions were determined by analysing STAT5 phosphorylation, antigen-specific cytokine release and by analysing markers of T-cell
exhaustion
and inflammation. Tuberculosis patients had lower soluble IL-7R (p < 0.001) and higher
IL-7
(p < 0.001) plasma concentrations as compared to healthy contacts. Both markers were largely independent and aberrant expression normalised during therapy and recovery. Furthermore, tuberculosis patients had lower levels of mIL-7R in T cells caused by post-transcriptional mechanisms. Functional in vitro tests indicated diminished
IL-7
-induced STAT5 phosphorylation and impaired
IL-7
-promoted cytokine release of Mycobacterium tuberculosis-specific CD4+ T cells from tuberculosis patients. Finally, we determined T-cell
exhaustion
markers PD-1 and SOCS3 and detected increased SOCS3 expression during therapy. Only moderate correlation of PD-1 and SOCS3 with
IL-7
expression was observed. We conclude that diminished soluble IL-7R and increased
IL-7
plasma concentrations, as well as decreased membrane-associated IL-7R expression in T cells, reflect impaired T-cell sensitivity to
IL-7
in tuberculosis patients. These findings show similarities to pathognomonic features of impaired T-cell functions and immune failure described in AIDS patients.
...
PMID:Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis. 2858 66
