Biological and clinical significance of T helper 17 cell deficiency: insight into monogenic defects

Abstract

T helper 17 (Th17) are a CD4+ T subpopulation cells which are involved in the host protection against microbes such as extracellular and intracellular bacteria, parasites, fungi, and viruses. Monogenic defects including those mutations in some genes such as the signal transducer and activator of transcription (STAT)1 and 3, dedicator of cytokinesis 8 (DOCK8), autoimmune regulator (AIRE), and interleukin 17 receptor A (IL-17RA) can lead to impairment in Th17 cell development and function along with the concomitant increased risk for chronic mucocutaneous candidiasis (CMC). The immunologic abnormalities in these patients include low frequency of Th17 cells; defective cutaneous or in vitro T cell response to Candida species, and/or autoantibodies against relevant cytokines. This review outlines the biological characteristics and functionality of Th17 cells, as well as the clinical features of individuals with genetic defects associated with Th17 deficiency.

Fasudil and SR1001 synergistically protect against sepsis-associated pancreatic injury by inhibiting RhoA/ROCK pathway and Th17/IL-17 response

“…The expression of RORγt has been detected in Th17 cells, and it has been shown to play a critical role in differentiation of Th17 cells. It is well known that signal transducer and activator of transcription 3 (STAT3) is a key transcription factor to regulate RORγt expression and involved in a variety of cellular biologic functions [ 41 , 42 ]. In the present study, consistent with the changes of Th17/IL-17, the expressions of p-STAT3 and RORγt were significantly increased in the model group, which be inhibited in the treatment group.…”

Mucocutaneous Candidiasis: Insights Into the Diagnosis and Treatment

“…In addition, in patients with reduced Th17 levels, altered lymphocyte proliferation in vitro and cytokine secretion could be observed in response to a stimulus with Candida. 106 However, patients with mutations of CARD9 generally do not present other defects of the humoral or cellular immunity, as with STAT3 LOF, DOCK8 and STAT1 GOF. Th17 levels are, instead, normal in the case of IL17RA/RC, IL17F and ACT1 mutation.…”

“…The dosage of IL-17A, IL-17F and IL-22 serum levels associated with the presence of anti-IL-17A, anti-IL-17F and anti-IL-22 autoantibodies and also against IFN can be useful in the diagnosis of APECED. 106 …”

“…The dosage of IL-17A, IL-17F and IL-22 serum levels associated with the presence of anti-IL-17A, anti-IL-17F and anti-IL-22 autoantibodies and also against IFN can be useful in the diagnosis of APECED. 106 Functional tests, such as a phosphorylation assay of STAT1, can help in early diagnosing the GOF mutation of STAT1 while Mucocutaneous Candidiasis awaiting the result of the genetic investigation or may be useful in evaluating the functional impact of a STAT1 mutation already identified. 38 In any case, genetic tests remain the gold standard in the diagnosis of diseases associated with CMC, specifically by the Sanger single gene study, the employment of gene panels or sequencing the entire exome.…”