Interleukin‐17 and Its Implication in the Regulation of Differentiation and Function of Hematopoietic and Mesenchymal Stem Cells

Abstract

Adult stem cells have a great potential applicability in regenerative medicine and cell-based therapies. However, there are still many unresolved issues concerning their biology, and the influence of the local microenvironment on properties of stem cells has been increasingly recognized. Interleukin (IL-) 17, as a cytokine implicated in many physiological and pathological processes, should be taken into consideration as a part of a regulatory network governing tissue-associated stem cells' fate. This review is focusing on the published data on the effects of IL-17 on the properties and function of hematopoietic and mesenchymal stem cells and trying to discuss that IL-17 achieves many of its roles by acting on adult stem cells.

Zinc Finger Protein 521 Regulates Early Hematopoiesis through Cell-Extrinsic Mechanisms in the Bone Marrow Microenvironment

“…It is notable that two proinflammatory cytokines, IFN-␥ and IL-17, were significantly elevated in the absence of ZFP521. Upregulation of IFN-␥ and that of IL-17 have each been linked with reduced hematopoietic stem cell function and increased myelopoiesis (59,60). IFN-␥ is associated with reduced erythropoiesis (61), which is supported by our detection of increased and decreased frequencies of GMP and MEP, respectively, in Zfp521-deficient mice.…”

“…Finally, many of the cytokines identified in the cytokine array are produced and secreted by BM niche cells, including osteoclasts and osteoblasts (60)(61)(62)(63)(64)(65)(66)(67)(68)(69). The developmental progression and function of these niche cells are known to be regulated by ZFP521, and their frequencies and function are altered in Zfp521 Ϫ/Ϫ mice (14)(15)(16)(17)30).…”

Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies

“…IL-17 is another pro-inflammatory cytokine that has been used for MSC priming in some studies. Increased proliferation of human and murine BM-MSC was demonstrated upon dose-dependent IL-17 priming [ 35 – 37 ]. In human MSC, this effect was dependent on the generation of reactive oxygen species (ROS) from the activation of the adapter molecule ACT-1 and TNF receptor-associated factor 6 (TRAF-6).…”

Network Pharmacology‐Based Investigation of the System‐Level Molecular Mechanisms of the Hematopoietic Activity of Samul‐Tang, a Traditional Korean Herbal Formula

“…e p53 signaling pathwaydependent complex interplay between cell cycle control, senescence, and apoptosis is closely involved in the modulation of HSC function and hematopoietic homeostasis [166][167][168][169][170][171]. Activation of IL-17 (a pro-inflammatory cytokine produced by distinct cluster of differentiation 4 + [CD4 + ] T helper 17 [ 17] cells)-associated pathway stimulates granulopoiesis by inducing the proliferation of bone marrow CD34 + cells and their differentiation into granulocytes; moreover, IL-17 inhibition might impair hematopoietic recovery and deteriorate myelotoxicity caused by radiation injury [172][173][174][175][176][177][178][179][180][181][182].…”