Lack of Type 2 Innate Lymphoid Cells Promotes a Type I-Driven Enhanced Immune Response in Contact Hypersensitivity

Rafei-Shamsabadi, David; Poel, Saskia van de; Dorn, Britta; Kunz, Stefanie; Martin, Stefan F.; Klose, Christoph S. N.; Arnold, Sebastian J.; Tanriver, Yakup; Ebert, Karolina; Diefenbach, Andreas; Halim, Timotheus Y.F.; McKenzie, Andrew N. J.; Jakob, Thilo

doi:10.1016/j.jid.2018.03.001

Cited by 32 publications

(38 citation statements)

References 48 publications

(76 reference statements)

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“…The development of type 1 ILCs requires the T-box transcription factor T-bet (Tbx21), and the development of type 2 ILCs requires the transcription factor GATA3 or retinoic acid receptor-related orphan nuclear receptor ␣ (ROR␣), whereas development of type 3 ILCs requires ROR␥t (10)(11)(12). Inbred C57BL/6 T-bet Ϫ/Ϫ (13), RoraFloxIL7RCre (14,15), and Ror␥t Ϫ/Ϫ mice (16) lack type 1 (17), type 2 (14), and type 3 ILCs (18), respectively, and were used as models for in vivo analysis of the effects of ILC deficiency.…”

mentioning

confidence: 99%

Roles of Type 1, 2, and 3 Innate Lymphoid Cells in Herpes Simplex Virus 1 InfectionIn VitroandIn Vivo

Hirose

Wang

Tormanen

et al. 2019

J Virol

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Innate lymphoid cells (ILCs) play important roles in host defense and inflammation. They are classified into three distinct groups based on their cytokine and chemokine secretion patterns and transcriptome profiles. Here, we show that ILCs isolated from mice can be infected with herpes simplex virus 1 (HSV-1) but that subsequent replication of the virus is compromised. After infection, type 2 ILCs expressed significantly higher levels of granulocyte colony-stimulating factor (G-CSF), interleukin 1α (IL-1α), IL-6, IL-9, RANTES, tumor necrosis factor alpha (TNF-α), CXCL1, CXCL2, CXCL10, CCL3, and CCL4 than infected type 1 or type 3 ILCs. Transcriptome-sequencing (RNA-seq) analysis of the ILCs 24 h after HSV-1 infection revealed that 77 herpesvirus genes were detected in the infected type 3 ILCs, whereas only 11 herpesvirus genes were detected in infected type 1 ILCs and 27 in infected type 2 ILCs. Compared with uninfected cells, significant upregulation of over 4,000 genes was seen in the HSV-1-infected type 3 ILCs, whereas 414 were upregulated in the infected type 1 ILCs and 128 in the infected type 2 ILCs. In contrast, in all three cell types, only a limited number of genes were significantly downregulated. Type 1, type 2, and type 3 ILC-deficient mice were used to gain insights into the effects of the ILCs on the outcome of ocular HSV-1 infection. No significant differences were found on comparison with similarly infected wild-type mice or on comparison of the three strains of deficient mice in terms of virus replication in the eyes, levels of corneal scarring, latency-reactivation in the trigeminal ganglia, or T-cell exhaustion. Although there were no significant differences in the survival rates of infected ILC-deficient mice and wild-type mice, there was significantly reduced survival of the infected type 1 or type 3 ILC-deficient mice compared with type 2 ILC-deficient mice. Adoptive transfer of wild-type T cells did not alter survival or any other parameters tested in the infected mice. Our results indicate that type 1, 2, and 3 ILCs respond differently to HSV-1 infection in vitro and that the absence of type 1 or type 3, but not type 2, ILCs affects the survival of ocularly infected mice. IMPORTANCE In this study, we investigated for the first time what roles, if any, innate lymphoid cells (ILCs) play in HSV-1 infection. Analysis of isolated ILCs in vitro revealed that all three subtypes could be infected with HSV-1 but that they were resistant to replication. The expression profiles of HSV-1-induced cytokines/chemokines and cellular and viral genes differed among the infected type 1, 2, and 3 ILCs in vitro. While ILCs play no role or a redundant role in the outcomes of latency-reactivation in infected mice, absence of type 1 and type 3, but not type 2, ILCs affects the survival of infected mice.

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mentioning

confidence: 99%

Roles of Type 1, 2, and 3 Innate Lymphoid Cells in Herpes Simplex Virus 1 InfectionIn VitroandIn Vivo

Hirose

Wang

Tormanen

et al. 2019

J Virol

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“…Furthermore, depletion of ILC2 resulted in substantially increased ear-swelling responses (Rafei-Shamsabadi et al, 2018). ILC2 cells express high levels of Arg1 and increase after resolution of CHS (Bi et al, 2017;Monticelli et al, 2016;Rafei-Shamsabadi et al, 2018). We hope that future studies will shed light on the contribution of the ILC Arg1/iNOS pathway to CHS responses.…”

Section: Innate Lymphoid Cellsmentioning

confidence: 92%

“…After allergen challenge in the murine CHS model, elevated numbers of ILC1 were detected in the skin, accompanied by increases in NK cells, IFN-g, and TNF-a. Furthermore, depletion of ILC2 resulted in substantially increased ear-swelling responses (Rafei-Shamsabadi et al, 2018). ILC2 cells express high levels of Arg1 and increase after resolution of CHS (Bi et al, 2017;Monticelli et al, 2016;Rafei-Shamsabadi et al, 2018).…”

Section: Innate Lymphoid Cellsmentioning

confidence: 98%

“…On the basis of cytokine production and transcription factor regulation, ILCs can be categorized into ILC1, ILC2, and ILC3 groupings, which parallel Th-cell subsets, with ILC2 the most prevalent in healthy skin (Spits et al, 2013). A recent study by Rafei-Shamsabadi et al (2018) suggests a key role of ILCs in the elicitation phase of ACD. After allergen challenge in the murine CHS model, elevated numbers of ILC1 were detected in the skin, accompanied by increases in NK cells, IFN-g, and TNF-a.…”

Section: Innate Lymphoid Cellsmentioning

confidence: 99%

“…Notably, neutrophils are thought to engage in cross-talk between both innate and adaptive immune cells, including macrophages, lymphocytes, and NK cells (Mantovani et al, 2011). It has been speculated that anti-CD90.2emediated ILC depletion could be facilitated by the presence of neutrophils in the skin, reinforcing the complex role of both ILCs and neutrophils in ACD (Rafei-Shamsabadi et al, 2018).…”

Section: Mast Cells Neutrophils Basophils and Eosinophilsmentioning

confidence: 99%

See 2 more Smart Citations

Shifting Paradigms in Allergic Contact Dermatitis: The Role of Innate Immunity

Brys

Rodriguez-Homs

Suwanpradid

et al. 2020

Journal of Investigative Dermatology

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The role of the innate immune system in allergic contact dermatitis (ACD) has traditionally been confined to the initial antigen sensitization phase. However, more recent findings have shown the role of innate immunity in additional aspects of ACD, including the effector phase of the classic type IV hypersensitivity reaction. As a result, the precise immunologic mechanisms mediating ACD are more complex than previously believed. The aim of this review is to provide insight into recent advances in understanding the role of the innate immune system in the pathogenesis of ACD, including novel mechanistic roles for macrophages, innate lymphoid cells, natural killer cells, innate gd T cells, and other signaling molecules. These insights provide new opportunities for therapeutic intervention in ACD.

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Requirement of RORα for maintenance and antitumor immunity of liver‐resident natural killer cells/ILC1s

Song

Wei

et al. 2021

Hepatology

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Backgroud and Aims: Liver type 1 innate lymphoid cells (ILC1s), also known as liver-resident natural killer (LrNK) cells, comprise a high proportion of total hepatic ILCs. However, factors regulating their maintenance and function remain unclear. Approach and Results: In this study, we found high expression of retinoidrelated orphan nuclear receptor alpha (RORα) in LrNK cells/ILC1s. Mice with conditional ablation of retinoid-related orphan nuclear receptor alpha (Rorα) in LrNK cells/ILC1s and conventional natural killer (cNK) cells had decreased LrNK cells/ILC1s but normal numbers of cNK cells. RORα-deficient LrNK cells/ILC1s displayed increased apoptosis and significantly altered transcriptional profile. Using a murine model of colorectal cancer liver metastasis, we found that RORα conditional deficiency resulted in more aggressive liver tumor progression and impaired effector molecule expression in LrNK cells/ ILC1s. Consequently, treatment with the RORα agonist efficiently limited liver metastases and promoted effector molecule expression of LrNK cells/ILC1s. Conclusions: This study reveals a role of RORα in LrNK cell/ILC1 maintenance and function, providing insights into the harnessing of LrNK cell/ILC1 activity in the treatment of liver cancer.

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Lack of Type 2 Innate Lymphoid Cells Promotes a Type I-Driven Enhanced Immune Response in Contact Hypersensitivity

Cited by 32 publications

References 48 publications

Roles of Type 1, 2, and 3 Innate Lymphoid Cells in Herpes Simplex Virus 1 InfectionIn VitroandIn Vivo

Roles of Type 1, 2, and 3 Innate Lymphoid Cells in Herpes Simplex Virus 1 InfectionIn VitroandIn Vivo

Shifting Paradigms in Allergic Contact Dermatitis: The Role of Innate Immunity

Requirement of RORα for maintenance and antitumor immunity of liver‐resident natural killer cells/ILC1s

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