Allergen-Experienced Group 2 Innate Lymphoid Cells Acquire Memory-like Properties and Enhance Allergic Lung Inflammation

Martínez-González, Itziar; Mathä, Laura; Steer, Catherine A.; Ghaedi, Maryam; Poon, Grace F. T.; Takei, Fumio

doi:10.1016/j.immuni.2016.06.017

Cited by 219 publications

(300 citation statements)

References 37 publications

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“…Several studies have shown that type 2 inflammation-associated cytokines can modulate the transcriptional activity and responses of multiple immune cell populations to subsequent stimuli (Halim et al, 2016; Martinez-Gonzalez et al, 2016). Thus, we hypothesized that sensory neurons would similarly respond to type 2 cytokines by altering their responsiveness to other pruritogens.…”

Section: Resultsmentioning

confidence: 99%

Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch

Oetjen

Mack

Feng

et al. 2017

Cell

722

786

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SUMMARY Mammals have evolved neurophysiologic reflexes such as coughing and scratching to expel invading pathogens and noxious environmental stimuli. It is well established that these responses are also associated with chronic inflammatory diseases such as asthma and atopic dermatitis. However, the mechanisms by which inflammatory pathways promote sensations such as itch remain poorly understood. Here, we show that type 2 cytokines directly activate sensory neurons in both mice and humans. Further, we demonstrate that chronic itch is dependent on neuronal IL-4Rα and JAK1 signaling. We also observe that patients with recalcitrant chronic itch that failed other immunosuppressive therapies markedly improve when treated with JAK inhibitors. Thus, signaling mechanisms previously ascribed to the immune system may represent novel therapeutic targets within the nervous system. Collectively, this study reveals an evolutionarily conserved paradigm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior.

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Section: Resultsmentioning

confidence: 99%

Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch

Oetjen

Mack

Feng

et al. 2017

Cell

722

786

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“…Although it is unknown why transient administration of IL-33 was sufficient for tumor development, a recent study showed that intranasal injection of IL-33 induced a sustained increase in lung ILC2s for more than 4 wk, albeit at a low level, and once ILC2s were primed by IL-33, they were highly responsive, even to unrelated allergens, and strongly induced inflammation (40). Thus, ILC2s primed by IL-33 may exert a long-term effect on the BD of KT-K19 CreERT mice.…”

Section: Discussionmentioning

confidence: 99%

Biliary epithelial injury-induced regenerative response by IL-33 promotes cholangiocarcinogenesis from peribiliary glands

Nakagawa

Suzuki

Hirata

et al. 2017

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

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The carcinogenic mechanism of extrahepatic cholangiocarcinoma (ECC) is unclear, due at least in part to the lack of an appropriate mouse model. Because human studies have reported frequent genetic alterations in the Ras-and TGFβ/SMAD-signaling pathways in ECC, mice with tamoxifen-inducible, duct-cell-specific Kras activation and a TGFβ receptor type 2 (TGFβR2) deletion were first generated by crossing LSL-Kras G12D , Tgfbr2 flox/flox , and K19 CreERT mice (KT-K19 CreERT ). However, KT-K19 CreERT mice showed only mild hyperplasia of biliary epithelial cells (BECs) in the extrahepatic bile duct (EHBD) and died within 7 wk, probably a result of lung adenocarcinomas. Next, to analyze the additional effect of E-cadherin loss, KT-K19 CreERT mice were crossed with CDH1 flox/flox mice (KTC-K19 CreERT ). Surprisingly, KTC-K19 CreERT mice exhibited a markedly thickened EHBD wall accompanied by a swollen gallbladder within 4 wk after tamoxifen administration. Histologically, invasive periductal infiltrating-type ECC with lymphatic metastasis was observed. Time-course analysis of EHBD revealed that recombined BECs lining the bile duct lumen detached due to E-cadherin loss, whereas recombined cells could survive in the peribiliary glands (PBGs), which are considered a BEC stem-cell niche. Detached dying BECs released high levels of IL-33, as determined by microarray analysis using biliary organoids, and stimulated inflammation and a regenerative response by PBGs, leading eventually to ECC development. Cell lineage tracing suggested PBGs as the cellular origin of ECC. IL-33 cooperated with Kras and TGFβR2 mutations in the development of ECC, and anti-IL-33 treatment suppressed ECC development significantly. Thus, this mouse model provided insight into the carcinogenic mechanisms, cellular origin, and potential therapeutic targets of ECC.extrahepatic cholangiocarcinoma | IL-33 | organoid | ILC2 | amphiregulin

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“…Interestingly, ILCs have been identified in the BM and the secondary lymphoid organs, and have been proposed to migrate from the intestine to the mesenteric lymph nodes [109] . Recent demonstrations of memory-like features of NK cells [16,17] and ILC2 [15] raise the possibility that the pool of ILCs is fundamentally altered through exposure to environmental challenges. A major question is whether ILCs, if long-lived, acquire epigenetic modifications consistent with the concept of "trained immunity" [76] or exhibit adaptive-like features of specificity as described for NK cells [16,17] .…”

Section: Innate Lymphoid Cellsmentioning

confidence: 99%

Cellular Innate Immunity: An Old Game with New Players

et al. 2016

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Innate immunity is a rapidly evolving field with novel cell types and molecular pathways being discovered and paradigms changing continuously. Innate and adaptive immune responses are traditionally viewed as separate from each other, but emerging evidence suggests that they overlap and mutually interact. Recently discovered cell types, particularly innate lymphoid cells and myeloid-derived suppressor cells, are gaining increasing attention. Here, we summarize and highlight current concepts in the field, focusing on innate immune cells as well as the inflammasome and DNA sensing which appear to be critical for the activation and orchestration of innate immunity, and may provide novel therapeutic opportunities for treating autoimmune, autoinflammatory, and infectious diseases.

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Allergen-Experienced Group 2 Innate Lymphoid Cells Acquire Memory-like Properties and Enhance Allergic Lung Inflammation

Cited by 219 publications

References 37 publications

Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch

Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch

Biliary epithelial injury-induced regenerative response by IL-33 promotes cholangiocarcinogenesis from peribiliary glands

Cellular Innate Immunity: An Old Game with New Players

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