IL-17A Influences Essential Functions of the Monocyte/Macrophage Lineage and Is Involved in Advanced Murine and Human Atherosclerosis

Erbel, Christian; Akhavanpoor, Mohammadreza; Okuyucu, Deniz; Wangler, Susanne; Dietz, Alex; Zhao, Li; Stellos, Konstantinos; Little, Kristina M.; Lasitschka, Felix; Doesch, Andreas O.; Hakimi, Maani; Dengler, Thomas J.; Giese, Thomas; Blessing, Erwin; Katus, Hugo A.; Gleissner, Christian A.

doi:10.4049/jimmunol.1400181

Cited by 128 publications

(98 citation statements)

References 43 publications

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“…Similarly, our study depicted an increased expression of Cox-2 and IL-17 upon BMSCTx in mice that was abrogated in the presence of celecoxib leading to enhanced engraftment of stem cells and wound closure.These results prompted us to elucidate the downstream mechanisms involved in Cox-2-mediated inflammation through IL-17. IL-17 is known to influence the essential functions of monocyte/macrophages in atherosclerosis [48]. Unlike other T-cell cytokines, IL-17 is known to elicit unique macrophage activation.…”

Section: Discussionmentioning

confidence: 99%

Cox-2 inhibition potentiates mouse bone marrow stem cell engraftment and differentiation-mediated wound repair

2017

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Section: Discussionmentioning

confidence: 99%

Cox-2 inhibition potentiates mouse bone marrow stem cell engraftment and differentiation-mediated wound repair

2017

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“…However, IL-17 has been reported to function as a monocyte chemokine, to promote monocyte adhesion and elicit a proinflammatory transcriptome in macrophages, suggesting direct signaling of this lineage may be involved. 113 Other proinflammatory cytokines coproduced by Tc17/Th17 such as GM-CSF 50 may contribute synergistically to macrophage differentiation/polarization at localized sites.…”

Section: Role Of Macrophages In Cgvhd Pathogenesismentioning

confidence: 99%

Chronic graft-versus-host disease: biological insights from preclinical and clinical studies

MacDonald¹,

Hill

Blazar

2017

Blood

235

217

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With the increasing use of mismatched, unrelated, and granulocyte colony-stimulating factor–mobilized peripheral blood stem cell donor grafts and successful treatment of older recipients, chronic graft-versus-host disease (cGVHD) has emerged as the major cause of nonrelapse mortality and morbidity. cGVHD is characterized by lichenoid changes and fibrosis that affects a multitude of tissues, compromising organ function. Beyond steroids, effective treatment options are limited. Thus, new strategies to both prevent and treat disease are urgently required. Over the last 5 years, our understanding of cGVHD pathogenesis and basic biology, born out of a combination of mouse models and correlative clinical studies, has radically improved. We now understand that cGVHD is initiated by naive T cells, differentiating predominantly within highly inflammatory T-helper 17/T-cytotoxic 17 and T-follicular helper paradigms with consequent thymic damage and impaired donor antigen presentation in the periphery. This leads to aberrant T- and B-cell activation and differentiation, which cooperate to generate antibody-secreting cells that cause the deposition of antibodies to polymorphic recipient antigens (ie, alloantibody) or nonpolymorphic antigens common to both recipient and donor (ie, autoantibody). It is now clear that alloantibody can, in concert with colony-stimulating factor 1 (CSF-1)-dependent donor macrophages, induce a transforming growth factor β–high environment locally within target tissue that results in scleroderma and bronchiolitis obliterans, diagnostic features of cGVHD. These findings have yielded a raft of potential new therapeutics, centered on naive T-cell depletion, interleukin-17/21 inhibition, kinase inhibition, regulatory T-cell restoration, and CSF-1 inhibition. This new understanding of cGVHD finally gives hope that effective therapies are imminent for this devastating transplant complication.

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“…ND: no data. report demonstrated synergistic or cross-tolerant effects of IL-17A and LPS on macrophage activation 12,13 . In addition, cross-inhibition of STAT3 between IL-6 and IL10 was reported 21 .…”

Section: Discussionmentioning

confidence: 93%

001 IL-17A induces heterogeneous macrophages, and it does not alter the effects of lipopolysaccharides on macrophage activation in the skin of mice

Nakai

Haba

et al. 2018

Journal of Investigative Dermatology

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Macrophages are central to inflammatory response and become polarized towards the M1 or M2 states upon activation by immunostimulants. In this study, we investigated the effects of lipopolysaccharides (LPS) and interleukin (IL)-In skin, various immune cells are activated by invading pathogens or skin damage. Macrophages are vital to innate immunity, and their activation leads to an increased capacity to regulate other cells through the release of cytokines and chemokines that is induced in adaptive immunity 1 . Persistent macrophage activity results in the development of chronic inflammatory skin diseases such as psoriasis and atopic dermatitis (AD) 2 . Abnormal immune conditions of tissues affects the activation and plasticity/polarization of macrophages (i.e. their maturation towards the M1 or M2 state) 3 . The classical pathway is defined as the interferon (IFN)-γ-dependent activation of M1 type macrophages by T helper 1 (Th1)-type responses. The alternative pathway is defined as the M2 type macrophage activation by Th2-type cytokines interleukin (IL)-4, IL-6, IL-10 and IL-13. However, recent studies have shown that the macrophage lineages are diverse and heterogeneous as demonstrated by the presence of unique M1/M2 heterogeneous macrophages in IL-17 immunity.IL-17 family members play an active role in inflammatory diseases and autoimmune diseases 4 . IL-17A is the prototype pro-inflammatory cytokine of the IL-17 family 5 , which is largely produced by activated memory T lymphocytes, and functions to stimulate innate immunity. A well-known IL-17A-related skin disease is psoriasis. The association between IL-17A and psoriasis is well established in humans, mouse and in vitro models 6 . The roles of IL-17A are also implicated in the pathogenesis of AD 7,8 . IL-17A is highly expressed in flaky-tail (Flg ft ) mouse, a murine AD model, that carries mutations in the filaggrin gene 9,10 . Moreover, IL-17A is involved in infectious, inflammatory, neutrophilic, granulomatous, bullous and malignant skin diseases 11 . However, there are few reports regarding the direct effects of IL-17A on the macrophage function in the skin.

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IL-17A Influences Essential Functions of the Monocyte/Macrophage Lineage and Is Involved in Advanced Murine and Human Atherosclerosis

Cited by 128 publications

References 43 publications

Cox-2 inhibition potentiates mouse bone marrow stem cell engraftment and differentiation-mediated wound repair

Cox-2 inhibition potentiates mouse bone marrow stem cell engraftment and differentiation-mediated wound repair

Chronic graft-versus-host disease: biological insights from preclinical and clinical studies

001 IL-17A induces heterogeneous macrophages, and it does not alter the effects of lipopolysaccharides on macrophage activation in the skin of mice

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