Current data on IL-17 and Th17 cells and implications for graft versus host disease

Abstract

Human interleukin 17 was first described in 1995 as a new cytokine produced primarily by activated T CD4+ cells that stimulate the secretion of IL-6 and IL-8 by human fibroblasts, besides increasing the expression of ICAM-1. Various authors have reported that IL-17A has a role in the protection of organisms against extracellular bacteria and fungi due to the capacity of IL-17A to recruit neutrophils to the areas of infection, evidencing a pathological role in various models of autoimmune diseases, such as experimental autoimmune encephalitis and arthritis. The participation of IL-17A has also been described in the acute rejection of organ transplants and graft versus host disease. However, the greatest revolution in research with IL-17 happened in 2000, when it was proposed that IL-17 cannot be classified as Th1 or Th2, but rather, simply as a new lineage of IL-17-producing T-cells. These findings modified the previously established Th1/Th2 paradigm, leading to the definition of the CD3+ CD4+ Th17 cellular subtype and establishment of a new model to explain the origin of various immune events, as well as its implication in the graft versus host disease that is discussed in depth in this article.

Comparative Analysis of Immunological Profiles in Women Undergoing Conventional and Single-Port Laparoscopic Cholecystectomy

“…IL-17A is involved in the protection of the organism against extracellular bacteria and fungi due to its capacity of recruiting neutrophils to the sites of infection. A pathological role of this cytokine has been demonstrated in various models of autoimmune diseases such as experimental autoimmune encephalitis and rheumatoid arthritis 22 .…”

Cellular and molecular mechanisms in graft-versus-host disease

“…The Th17 percentage and RORgt expression were significantly higher, whereas T reg percentage and Foxp3 expression were significantly lower in severe aGVHD (grades 3-4) and mild aGVHD (grades 1-2) patients than in aGVHD (grade 0) patients and healthy donors. Parallel to those findings, T reg expansion has been shown to be capable of reducing the severity of aGVHD in murine models [39,40].The dynamic balance between the Th17 and Foxp3 + T regs and the changes of Th17-associated cytokines could be the indicators of the disease progression and prognostic biomarkers of aGVHD [41,42]. Adoptive transfer of T regs can prevent GVHD in rodents, suggesting a therapeutic potential of T regs for GVHD in humans.…”

IL-17A exacerbates cisplatin-based resistance of OVCA via upregulating the expression of ABCG2 and MDR1 through Gli1-mediated Hh signaling

“…About IL-17A-producing cells, other investigator's previous studies showed although IL-17A was initially hypothesized to be secreted primarily by Th17 cells, some non-Th17 cells can also produce IL-17A, such as macrophages, eosinophils, neutrophils, monocytes and CD8 + T cells [4][5][6]. In our present study, IHC staining for IL-17A in the clinical specimens indicated that IL-17-positive cells, according to morphological characteristics of cells, in ovarian cancer environment, included big irregular-shaped macrophages and small round lymphocytes and other types of cells (Figure 7).…”

“…Although IL-17A was initially hypothesized to be secreted primarily by Th17 cells, some other cells can also produce IL-17A, such as macrophages, eosinophils, neutrophils, monocytes and CD8 + T cells [4][5][6]. In addition, it had been reported that IL-17A could be detected in a variety of human tumors frequently [7], including gastric adenocarcinoma [8], non-small-cell lung carcinoma (NSCLC) [9], hepatocellular carcinoma (HCC) [10,11], colorectal carcinoma [12], cervical cancer [13], and ovarian cancer (OVCA) [14,15].…”