SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling

Cortez, Victor S.; Ulland, Tyler K.; Cervantes-Barragán, Luisa; Bando, Jennifer K.; Robinette, Michelle L.; Wang, Qianli; White, Andrew J.; Gilfillan, Susan; Cella, Marina; Colonna, Marco

doi:10.1038/ni.3809

Cited by 263 publications

(294 citation statements)

References 44 publications

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“…MCMV infection also induces significant body weight loss. The magnitude of body weight loss is correlated with severity of viral infection . We next determined how alcohol consumption affects body weight change during the acute phase of MCMV infection.…”

Section: Resultsmentioning

confidence: 99%

Chronic alcohol consumption exacerbates murine cytomegalovirus infection via impairing nonspecific and specific NK activation in mice

Little

Zhang

et al. 2018

FASEB BioAdvances

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Chronic alcohol consumption increases the susceptibility to infectious diseases by compromising the immune system. Cytomegalovirus infection is common in humans and usually is asymptomatic in immunocompetent people. However, it can induce life‐threatening medical complications in immunocompromised individuals such as alcoholics. How chronic alcohol consumption exacerbates cytomegalovirus infection is not known. Herein, we used a mouse cytomegalovirus model to study the underlying cellular and molecular mechanism. We found that alcohol consumption increased viral titers in spleen after 4 days of infection, enhanced body weight loss and inhibited splenomegaly during the acute phase of infection. Blood level of IFN‐β, splenic IFN‐γ and granzyme B‐producing NK cells were lower in alcohol‐consuming mice than in water‐drinking mice at 12 hours after viral infection. Moreover, alcohol consumption decreased IL‐15‐producing DC after 36 hours infection, inhibited NK cell, specifically Ly49H+ NK cell maturation and proliferation 3‐6 days after viral infection. Surprisingly, alcohol consumption enhanced NK cell and CD8+ T‐cell continuous activation and increased granzyme B‐producing cells. However, alcohol consumption decreased the expression of perforin in spleen and liver. Taken together, chronic alcohol consumption exacerbates cytomegalovirus infection via impairing nonspecific and specific NK cell activation, specifically IFN‐γ and perforin production.

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Section: Resultsmentioning

confidence: 99%

Chronic alcohol consumption exacerbates murine cytomegalovirus infection via impairing nonspecific and specific NK activation in mice

Little

Zhang

et al. 2018

FASEB BioAdvances

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“…11,12 Despite the effector potential of NK cells, they are usually dysfunctional in the tumour microenvironment. 16,17 Studies have proven the concept of, and have shown the potentials of, targeting some pathways for the reinvigoration of NK cell anti-tumour immunity. 16,17 Studies have proven the concept of, and have shown the potentials of, targeting some pathways for the reinvigoration of NK cell anti-tumour immunity.…”

Section: Nk Cells Are Anti-tumour Effector Cells Usually Dysfunctionamentioning

confidence: 99%

Genetic reprogramming for NK cell cancer immunotherapy with CRISPR/Cas9

Afolabi

Adeshakin

Sani³

et al. 2019

Immunology

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Summary Natural killer cells are potent cytotoxic lymphocytes specialized in recognizing and eliminating transformed cells, and in orchestrating adaptive anti‐tumour immunity. However, NK cells are usually functionally exhausted in the tumour microenvironment. Strategies such as checkpoint blockades are under investigation to overcome NK cell exhaustion in order to boost anti‐tumour immunity. The discovery and development of the CRISPR/Cas9 technology offer a flexible and efficient gene‐editing capability in modulating various pathways that mediate NK cell exhaustion, and in arming NK cells with novel chimeric antigen receptors to specifically target tumour cells. Despite the high efficiency in its gene‐editing capability, difficulty in the delivery of the CRISPR/Cas9 system remains a major bottleneck for its therapeutic applications, particularly for NK cells. The current review discusses feasible approaches to deliver the CRISPR/Cas9 systems, as well as potential strategies in gene‐editing for NK cell immunotherapy for cancers.

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“…The presence of TGF‐β in the tumor microenvironment has been shown to decrease the responsiveness of NK cells, and it is also required for CD103 + tissue‐resident ILCs correct differentiation in many other tissues . A TGFβ‐dependent tumor immunoescape mechanism has been suggested as a NK cell transdifferentiation into non‐cytotoxic ILC1s consequences . Also in the PyMT‐driven tumors, both NK cells expressing Eomes and CD49a + and non‐NK ILC1‐like cells can be suppressed via TGFβ signals .…”

Section: Double‐edged Role Of Ilcs In Cancermentioning

confidence: 99%

Progression or suppression: Two sides of the innate lymphoid cells in cancer

Hosseini

Sharafkandi

Seyfizadeh

et al. 2019

J of Cellular Biochemistry

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Innate lymphoid cells (ILCs) as key players in innate immunity have been shown to be significantly associated with inflammation, lymphoid neogenesis, tissue remodeling, mucosal immunity and lately have been considered a remarkable nominee for either tumor‐promoting or tumor‐inhibiting functions. This dual role of ILCs, which is driven by intrinsic and extrinsic factors like plasticity of ILCs and the tumor microenvironment, respectively, has aroused interest in ILCs subsets in past decade. So far, numerous studies in the cancer field have revealed ILCs to be key players in the initiation, progression and inhibition of tumors, therefore providing valuable insights into therapeutic approaches to utilize the immune system against cancer. Herein, the most recent achievements regarding ILCs subsets including new classifications, their transcription factors, markers, cytokine release and mechanisms that led to either progression or inhibition of many tumors have been evaluated. Additionally, the available data regarding ILCs in most prevalent cancers and new therapeutic approaches are summarized.

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SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling

Cited by 263 publications

References 44 publications

Chronic alcohol consumption exacerbates murine cytomegalovirus infection via impairing nonspecific and specific NK activation in mice

Chronic alcohol consumption exacerbates murine cytomegalovirus infection via impairing nonspecific and specific NK activation in mice

Genetic reprogramming for NK cell cancer immunotherapy with CRISPR/Cas9

Progression or suppression: Two sides of the innate lymphoid cells in cancer

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