Macrophages participate in IL‐17‐mediated inflammation

Barin, Jobert G.; Baldeviano, G. Christian; Talor, Monica V.; Wu, Lei; Ong, SuFey; Quader, Farhan; Chen, Ping; Zheng, Dongfeng; Caturegli, Patrizio; Rose, Noel R.; Čiháková, Daniela

doi:10.1002/eji.201141737

Cited by 95 publications

(83 citation statements)

References 43 publications

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“…SPMs are mobilized from blood monocytes, whereas LPMs are maintained independently of hematopoiesis (34). Importantly, IL-17 has previously been shown to recruit blood monocytes (46,47), as well as mature macrophages (48)(49)(50) to various tissues; and we have detected high levels of Il17ra selectively on SPMs isolated from ID8-bearing animals. Thus, our work identifies a link between IL-17-secreting γδ T cells and the mobilization/expansion of SPMs in the peritoneal cavity.…”

Section: Discussionmentioning

confidence: 57%

Murine CD27 ⁽⁻⁾ Vγ6 ⁽⁺⁾ γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages

Rei

Gonçalves-Sousa

Lança

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

179

199

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Cancer-associated inflammation mobilizes a variety of leukocyte populations that can inhibit or enhance tumor cell growth in situ. These subsets include γδ T cells, which can infiltrate tumors and typically provide large amounts of antitumor cytokines, such as IFN-γ. By contrast, we report here that in a well-established transplantable (ID8 cell line) model of peritoneal/ovarian cancer, γδ T cells promote tumor cell growth. γδ T cells accumulated in the peritoneal cavity in response to tumor challenge and could be visualized within solid tumor foci. Functional characterization of tumor-associated γδ T cells revealed preferential production of interleukin-17A (IL-17), rather than IFN-γ. Consistent with this finding, both T cell receptor (TCR)δ-deficient and IL-17-deficient mice displayed reduced ID8 tumor growth compared with wild-type animals. IL-17 production by γδ T cells in the tumor environment was essentially restricted to a highly proliferative CD27 (−) subset that expressed Vγ6 instead of the more common Vγ1 and Vγ4 TCR chains. The preferential expansion of IL-17-secreting CD27 (−) Vγ6 (+) γδ T cells associated with the selective mobilization of unconventional small peritoneal macrophages (SPMs) that, in comparison with large peritoneal macrophages, were enriched for IL-17 receptor A, and for protumor and proangiogenic molecular mediators, which were upregulated by IL-17. Importantly, SPMs were uniquely and directly capable of promoting ovarian cancer cell proliferation. Collectively, this work identifies an IL-17-dependent lymphoid/myeloid crosstalk involving γδ T cells and SPMs that promotes tumor cell growth and thus counteracts cancer immunosurveillance. gamma-delta T cells | tumor immunologyD eveloping tumors are infiltrated by a variety of leukocyte subsets that can either promote or inhibit inflammation, and thus impact on cancer progression (1). Among such populations are γδ T cells, which are major players in lymphoid stress surveillance likely due to their recognition of stress-inducible molecules independently of MHC-mediated antigen presentation (2). Moreover, abundant IFN-γ secretion and cytotoxic effector functions endow γδ T cells with potent antitumor activity. This has been clearly documented in murine models of spontaneous (3), chemically induced (4), transgenic (5), and transplantable (6, 7) tumors. For example, in the widely used B16 melanoma model, γδ T cells were shown to infiltrate tumors very early and provided a critical source of IFN-γ that significantly delayed tumor growth (6, 7).Human γδ T cells also possess IFN-γ-secreting potential, which is displayed immediately at birth (8) and display cytotoxicity against tumor lines of diverse origin, including epithelial (9, 10) and hematological (11,12) tumors. This has prompted the development of cancer clinical trials targeting γδ T cells, which have produced encouraging, albeit highly variable, degrees of therapeutic responses (13-15). There is therefore great interest in maximizing the antitumor functions of γδ T cells for cancer ...

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Section: Discussionmentioning

confidence: 57%

Murine CD27 ⁽⁻⁾ Vγ6 ⁽⁺⁾ γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages

Rei

Gonçalves-Sousa

Lança

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

179

199

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“…The expression levels of chIL-17RA were unchanged or decreased significantly in splenic lymphocytes stimulated with ConA, LPS, or poly(I·C). Similarly, after LPS stimulation, mouse IL-17RA is significantly reduced in bone marrow-derived macrophages, but the expression levels are unchanged in poly(I·C) (45). In contrast, rainbow trout IL-17RA transcript increases in head kidney primary leukocytes activated with poly(I·C) but do not change with LPS stimulation (40).…”

Section: Discussionmentioning

confidence: 96%

Downregulation of Chicken Interleukin-17 Receptor A during Eimeria Infection

et al. 2014

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e Both interleukin-17A (IL-17A) and IL-17F are proinflammatory cytokines that have an important role in intestinal homeostasis via receptor signaling. These cytokines have been characterized in chickens, but very little is known about their receptors and their functional activity. We provide here the first description of the sequence analysis, bioactivity, and comparative expression analysis of chicken IL-17RA (chIL-17RA) in chickens infected with Salmonella and Eimeria, two major infectious agents of gastrointestinal diseases of poultry of economic importance. A full-length chIL-17RA cDNA with a 2,568-bp coding region was identified from chicken thymus cDNA. chIL-17RA shares ca. 46% identity with mammalian homologues and 29.2 to 31.5% identity with its piscine counterparts. chIL-17RA transcript expression was relatively high in the thymus and in the chicken macrophage cell line HD11. The chIL-17RA-specific small interfering RNA inhibits interleukin-6 (IL-6), IL-8, and IL-1␤ mRNA expression in chicken embryo fibroblast cells (but not in DF-1 cells) stimulated with chIL-17A or chIL-17F. Interaction between chIL-17RA and chIL-17A was confirmed by coimmunoprecipitation. Downregulation of chIL-17RA occurred in concanavalin A-or lipopolysaccharide-activated splenic lymphocytes but not in poly(I·C)-activated splenic lymphocytes. In Salmonella-and Eimeria-infected chickens, the expression levels of the chIL-17RA transcript were downregulated in intestinal tissues from chickens infected with two Eimeria species, E. tenella or E. maxima, that preferentially infect the cecum and jejunum, respectively. However, chIL-17RA expression was generally unchanged in Salmonella infection. These results suggest that chIL-17RA has an important role in mucosal immunity to intestinal intracellular parasite infections such as Eimeria infection.

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“…During nasopharyngeal colonization, mir155KO mice exhibited lower nasopharyngeal IL-17A mRNA levels and reduced splenic Th17 numbers and IL-17A secretion upon restimulation with S. pneumoniae. A reduction of Th17 cells and IL-17A production in the nasopharynx would abrogate macrophage recruitment since IL-17A is a potent chemotactic factor for both monocytes (34) and macrophages (35,36). Another important chemotactic factor for these cells, MCP-1 (CCL2), was also investigated in the nasopharynxes of WT and mir155KO mice; however, no differences were observed.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-155 Is Required for Clearance of Streptococcus pneumoniae from the Nasopharynx

et al. 2014

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Pneumonia caused by؉ T-cell responses in vivo, lower IL-17A mRNA levels in the nasopharynx, and a reduced capacity to induce Th17 cell polarization. Given that knockout mice are also limited in the capacity to generate high-titer S. pneumoniae-specific antibodies, we conclude that mir-155 is a critical mediator of the cellular effectors needed to clear primary and secondary S. pneumoniae colonizations.

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Macrophages participate in IL‐17‐mediated inflammation

Cited by 95 publications

References 43 publications

Murine CD27 ⁽⁻⁾ Vγ6 ⁽⁺⁾ γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages

Murine CD27 ⁽⁻⁾ Vγ6 ⁽⁺⁾ γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages

Downregulation of Chicken Interleukin-17 Receptor A during Eimeria Infection

MicroRNA-155 Is Required for Clearance of Streptococcus pneumoniae from the Nasopharynx

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Macrophages participate in IL‐17‐mediated inflammation

Cited by 95 publications

References 43 publications

Murine CD27 (−) Vγ6 (+) γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages

Murine CD27 (−) Vγ6 (+) γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages

Downregulation of Chicken Interleukin-17 Receptor A during Eimeria Infection

MicroRNA-155 Is Required for Clearance of Streptococcus pneumoniae from the Nasopharynx

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Murine CD27 ⁽⁻⁾ Vγ6 ⁽⁺⁾ γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages

Murine CD27 ⁽⁻⁾ Vγ6 ⁽⁺⁾ γδ T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages