Effect of IL-17 onIn VitroHematopoietic Progenitor Cells Growth and Cytokine Release in Normal and Post-irradiated Murine Bone Marrow

Abstract

The influence of recombinant human IL-17 on granulocyte-macrophage (CFU-GM) and erythroid (BFU-E and CFU-E) progenitors and the release of IL-la/fl, IL-6 and erythropoietin (EPO) was estimated in the bone marrow cells obtained from normal and sublethally irradiated mice. In normal mice IL-17 increased CFU-GM and BFU-E and reduced CFU-E derived colonies numbers and augmented release of ILL-6 and EPO. In irradiated mice the effects of IL-17 on hematopoietic progenitors were lineage-dependent, as well as dependent on their stage of differentiation and the time after the irradiation. IL-17 had no major effects on CFU-GM on day 1 and 3, but decreased their number on day 2, while enhanced both BFU-E and CFU-E on day 1 and 2 after irradiation, whereas on day 3 its effect on erythroid progenitors was again as observed in normal mice. After irradiation, IL-17 increased the release of IL-la, IL-6 and EPO. The observed effects suggested the involvement of IL-17 in the regulation of hematopoiesis and indicated that its effects on both hematopoietic progenitors and cytokine release are dependent on the physiological/ pathological status of the organism.

Haplotype of non-synonymous mutations within IL-23R is associated with susceptibility to severe malaria anemia in a P. falciparum holoendemic transmission area of Kenya

“…However, the complex interplay between successfully controlling an infection and the generation of inflammatory-derived anemia during a malaria infection is difficult to discern at the molecular level [62]. IL-17 is a prototypical example of such complexity since IL-17 bridges immune and hematopoietic regulation by stimulating early stage erythroid progenitors (i.e., burst forming unit erythroid, BFU-E) [63], and in the opposite context, inhibits late stage erythroid progenitors [30, 64, 65]. Further studies are required to delineate the influence of genetic polymorphisms within IL-23R on differential expression and production of inflammatory mediators to unravel the molecular mechanisms through which the IL-23/T-helper 17 axis collectively influences the development of malarial disease outcomes.…”

“…IL-17 is produced by activated T-cells and is involved in priming of T-cells through its ability to stimulate macrophages and some epithelial cells to produce pro-inflammatory mediators [e.g., IL-1, IL-6, TNF-α, NOS-2, metalloproteases known to be important in inflammatory diseases [26, 27]. IL-17 is also important in linking immune responses with erythropoiesis through its ability to enhance proliferation of erythroid precursor cells [28–30]. Although IL-17 has not previously been explored during malaria mono-infection in the cohort of children investigated here, we have shown that IL-17 has a significant positive association with Hb in malaria-infected children with HIV-1 [31].…”

Elevating body temperature enhances hematopoiesis and neutrophil recovery after total body irradiation in an IL-1–, IL-17–, and G-CSF–dependent manner

“…IL-17 signaling regulates G-CSF expression, as well as the expression of other cytokines that increase circulating neutrophil numbers. 25,27,[34][35][36] The effect of IL-17 on neutrophil numbers stems from its ability to increase G-CSF mRNA stability that ultimately leads to a systemic increase in G-CSF concentrations. 23 Mice lacking IL-17 have previously been shown to be more sensitive to TBI than normal mice in that they have a reduced LD 50 from 8.5 Gy in female C57BL/6 mice to 7.25 Gy in female IL17ra Ϫ/Ϫ mice and also experience increased myelotoxicity after radiation confirming an important role of IL-17 in protection from radiation-induced hematologic damage.…”

Linking immunity and hematopoiesis by bone marrow T cell activity

“…It has been shown that oncostatin M and IL-17 produced by T cells can stimulate IL-6 production by endothelial cells and osteocytes (32,36). IL-6 has an important effect on neutrophil production.…”

“…Indeed, CD4 + T cells are wonderful cytokine producers, not only quantitatively, but also qualitatively, including the major T cell cytokines that control the immune responses such as IFN-γ, IL-4, IL-5, IL-13, IL-10 and TGF-ß, and the "minor" cytokines, whose effects on adaptive immune responses are less prominent (29). This group includes GM-CSF, IL-3, IL-6, IL-17, and oncostatin M -all involved in the regulation of hematopoiesis (30)(31)(32)(33)(34)(35)(36)(37). The major problem is that most of these cytokines are not T cell exclusive.…”