Enhanced IL‐10 production by CD4<sup>+</sup> T cells primed in IL‐15Rα‐deficient mice

Chow, Kai-Ping N.; Lee, Jan-Mou; Qiu, Jian Tai; Liao, Shuen‐Kuei; Lin, Shih‐Chieh; Hsu, Shuo-Lun; Wu, Ningning; Lin, Yen‐Fu; Wu, Tzong‐Shoon

doi:10.1002/eji.201141746

Cited by 6 publications

(6 citation statements)

References 45 publications

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“…However, this study did not investigate the status of epithelial cell damage, subsequent regeneration, and the role of IL-22. It is also important to note that the lack of IL-15Rα has been implicated in enhanced production of IL-10 44 . Thus, an overall reduction in the mortality could be attributed to a reduced recruitment of T cells that results in significantly less inflammation and pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection

Kumar

Thakar

Ouyang³

et al. 2013

Mucosal Immunology

158

174

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Influenza infection primarily targets the upper respiratory system, leading to a severe destruction of the epithelial cell layer. The role of immune cells in the regeneration of tracheal and bronchial epithelial cells is not well defined. Here, we investigated the production of pro-constructive cytokine, Interleukin-22 (IL-22), in the bronchoalveolar lavage (BAL), trachea, lung tissue, and spleen during influenza infection. We found that conventional NK cells (NCR1+NK1.1+CD127−RORγt−) were the predominant IL-22-producers in the BAL, trachea and lung tissues. Tracheal epithelial cells constitutively expressed high levels of IL-22R and underwent active proliferation in response to IL-22 in the wild type (WT) mice. Infection of IL-22−/− mice with influenza virus resulted in a severe impairment in the regeneration of tracheal epithelial cells. In addition, IL-22−/− mice continued to lose body weight even after 10 days post infection (DPI 10) without any recovery. Tracheal epithelial cell proliferation was significantly reduced in IL-22−/− mice during influenza infection. Adoptive transfer of IL-22 sufficient but not IL-22 deficient NK cells into IL-22−/− mice restored the tracheal/bronchial epithelial cell regeneration and conferred protection against inflammation. Our findings strongly suggest that conventional NK cells have evolved to both kill virus-infected cells and also to provide vital cytokines for tissue regeneration.

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Section: Discussionmentioning

confidence: 99%

IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection

Kumar

Thakar

Ouyang³

et al. 2013

Mucosal Immunology

158

174

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“…BM-DCs were cultured and prepared as previously described. [69][70] Briefly, total BM cells were collected from the femurs and tibias of BALB/c mice and depleted of red blood cells with ACK lysis buffer (0.15 M NH 4 Cl, 1 mM KHCO 3 , 0.1 mM EDTA, pH 7.2). Cells were then cultured in complete RPMI-1640 medium supplemented with 20 ng/mL CSF2 (Peprotech, 315-03), 10% fetal bovine serum, 50 mM 2-ME (Gibco TM , 21985023), 100 unit/mL penicillin, and 100 mg/mL streptomycin (Gibco TM , 15140122) in a humidified 5% CO 2 incubator at 37 C. On d 3, 30 mL fresh media with 20 ng/mL CSF2 was added.…”

Section: Bm-dc Preparationmentioning

confidence: 99%

Necroptosis promotes autophagy-dependent upregulation of DAMP and results in immunosurveillance

et al. 2017

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Programmed necrosis, necroptosis, is considered to be a highly immunogenic activity, often mediated via the release of damage-associated molecular patterns (DAMPs). Interestingly, enhanced macroautophagic/autophagic activity is often found to be accompanied by necroptosis. However, the possible role of autophagy in the immunogenicity of necroptotic death remains largely obscure. In this study, we investigated the possible mechanistic correlation between phytochemical shikonin-induced autophagy and the shikonin-induced necroptosis for tumor immunogenicity. We show that shikonin can instigate RIPK1 (receptor [TNFRSF]-interacting serine-threonine kinase 1)- and RIPK3 (receptor-interacting serine-threonine kinase 3)-dependent necroptosis that is accompanied by enhanced autophagy. Shikonin-induced autophagy can directly contribute to DAMP upregulation. Counterintuitively, among the released and ectoDAMPs, only the latter were shown to be able to activate the cocultured dendritic cells (DCs). Interruption of autophagic flux via chloroquine further upregulated ectoDAMP activity and resultant DC activation. For potential clinical application, DC vaccine preparations treated with tumor cells that were already pretreated with chloroquine and shikonin further enhanced the antimetastatic activity of 4T1 tumors and reduced the effective dosage of doxorubicin. The enhanced immunogenicity and vaccine efficacy obtained via shikonin and chloroquine cotreatment of tumor cells may thus constitute a compelling strategy for developing cancer vaccines via the use of a combinational drug treatment.

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“…19,35 Our results ( Figure 5) confirm the observation that the absence of IL-15 does not alter the frequency of Tregs. 36 On the other hand, BDC2.5 TCR Tg CD4 1 T cells that had expanded in the absence of IL-15 showed reduced antigeninduced differentiation into IFN-c producing cells (Figure 7). Despite the reduction in IFN-c production, the ability of BDC2.5 cells to induce T1D in NOD.scid.Il15 2/2 recipients 21 suggests that increase in the frequency of autoantigen specific T cells, as observed with TCR Tg mice, may overcome the critical threshold of islet-antigen specific T cells required to cause pathology.…”

Section: Discussionmentioning

confidence: 96%

“…For instance, it has been shown that lack of IL-15 skewed the antigen specific CD4 1 T cells to produce IL-10 or IL-17. 36,37 Accordingly, autoimmune diseases mediated by Th17 cells such as experimental autoimmune encephalomyelitis are aggravated by the absence of IL-15. 36,37 In this study, we have identified a novel role for IL-15 in restraining the homeostatic expansion of CD4 1 T cells.…”

Section: Discussionmentioning

confidence: 99%

“…36,37 Accordingly, autoimmune diseases mediated by Th17 cells such as experimental autoimmune encephalomyelitis are aggravated by the absence of IL-15. 36,37 In this study, we have identified a novel role for IL-15 in restraining the homeostatic expansion of CD4 1 T cells. Thus, IL-7 and IL-15, the two major cytokines that regulate the survival and homeostasis of different subsets of T cells also restrain the expansion of CD4 1 T cells.…”

Section: Discussionmentioning

confidence: 99%

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IL-15 trans-presentation regulates homeostasis of CD4+ T lymphocytes

et al. 2014

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Interleukin-15 (IL-15) is essential for the survival of memory CD8(+) and CD4(+) T cell subsets, and natural killer and natural killer T cells. Here, we describe a hitherto unreported role of IL-15 in regulating homoeostasis of naive CD4(+) T cells. Adoptive transfer of splenocytes from non-obese diabetic (NOD) mice results in increased homeostatic expansion of T cells in lymphopenic NOD.scid.Il15(-/-) mice when compared to NOD.scid recipients. The increased accumulation of CD4(+) T cells is also observed in NOD.Il15(-/-) mice, indicating that IL-15-dependent regulation also occurs in the absence of lymphopenia. NOD.scid mice lacking the IL-15Rα chain, but not those lacking the common gamma chain, also show increased accumulation of CD4(+) T cells. These findings indicate that the IL-15-mediated regulation occurs directly on CD4(+) T cells and requires trans-presentation of IL-15. CD4(+) T cells expanding in the absence of IL-15 signaling do not acquire the characteristics of classical regulatory T cells. Rather, CD4(+) T cells expanding in the absence of IL-15 show impaired antigen-induced activation and IFN-γ production. Based on these findings, we propose that the IL-15-dependent regulation of the naive CD4(+) T-cell compartment may represent an additional layer of control to thwart potentially autoreactive cells that escape central tolerance, while permitting the expansion of memory T cells.

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Enhanced IL‐10 production by CD4⁺ T cells primed in IL‐15Rα‐deficient mice

Abstract: In this study, we investigated the functional outcomes of CD4

Cited by 6 publications

References 45 publications

IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection

IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection

Necroptosis promotes autophagy-dependent upregulation of DAMP and results in immunosurveillance

IL-15 trans-presentation regulates homeostasis of CD4+ T lymphocytes

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Enhanced IL‐10 production by CD4+ T cells primed in IL‐15Rα‐deficient mice

Abstract: In this study, we investigated the functional outcomes of CD4

Cited by 6 publications

References 45 publications

IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection

IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection

Necroptosis promotes autophagy-dependent upregulation of DAMP and results in immunosurveillance

IL-15 trans-presentation regulates homeostasis of CD4+ T lymphocytes

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Enhanced IL‐10 production by CD4⁺ T cells primed in IL‐15Rα‐deficient mice