Research progress of type Ⅱ innate lymphocytes

Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences››2022,Vol. 43››Issue (9): 666-673.DOI:10.3969/j.issn.2097-0005.2022.09.002

• Invited Monographs •Previous Articles Next Articles

Research progress of type Ⅱ innate lymphocytes

Xinyue XU¹(), Xiuli JING², Hua TANG³()

^1.School of Clinical and Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences，Jinan 250117，China
^2.School of Chemical and Pharmaceutical Engineering, Shandong First Medical University & Shandong Academy of Medical Sciences，Jinan 250117，China
^3.Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences，Jinan 250117，China

Received:2022-05-02Online:2022-09-25Published:2022-11-03
Contact:Hua TANG

Ⅱ型固有淋巴细胞的研究进展

徐心悦¹(), 景秀丽², 唐华³()

^1.betway必威登陆网址（betway.com ），临床与基础医学院
^2.化学与制药工程学院
^3.医学科技创新中心，山东济南 250117

通讯作者:唐华
作者简介:徐心悦，硕士研究生，研究方向：细胞免疫，E-mail：910893566@qq.com。
唐华，二级岗位教授，浙江大学肿瘤学博士，美国EMORY大学博士后，山东省引进海外高层次创新人才和泰山学者海外特聘专家，山东省有突出贡献的中青年专家，山东省留学人员回国创业奖获得者。唐华博士为中国免疫学会会员、山东省免疫学会第六届常务理事。多年来从事树突状细胞的研究，特别关注该细胞对获得性免疫的调控在人类重大免疫相关性疾病中的作用。于2010年底回国到betway必威登陆网址泰安校区（原泰山医学院）组建研究团队，2021年被聘为校医学科技创新中心PI。指导团队累计获得24项国家级课题（共1 700余万元，达2.3项/人，130余万元/人），其中包括唐华博士自己主持的“973”课题（2015CB943203）、国家自然科学基金重大研究计划（92042306）和三项国家自然科学基金面上项目。获国家发明专利2项，以第一作者或通讯作者在Nature Immunology、Nature Communications、Blood、Cancer Letters、eBiomedicine等杂志上发表SCI论文多篇。
基金资助:
山东省自然科学基金(ZR2018LC009);山东省医药卫生科技发展计划(2017WS426)

Abstract

Abstract:

Type Ⅱ innate lymphoid cells （ILC2s） are a group of innate immune cells that have similar functions to type Ⅱ helper T cells （Th2） and can rapidly secrete Th2 cytokines. They play an important role in type 2 immunity. ILC2s can receive signals from epithelial cells， stromal cells， nerve cells and other immune cells， and then regulate the function of downstream effector cells， thus exerting important effector functions in barrier tissues， such as lung and skin. In this paper， the classification， development and main functions of ILC2s will be summarized， and the main research progress of ILC2s in recent years will be reviewed.

Key words:ILC2s,asthma,tumor,metabolism

摘要：

Ⅱ型固有淋巴细胞（type Ⅱ innate lymphoid cells， ILC2s）是一群具有与Ⅱ型辅助性T细胞（type Ⅱ helper T cells， Th2）功能相似、能快速分泌Th2型细胞因子的固有免疫细胞，在2型免疫反应（type 2 immunity）中具有重要作用。ILC2s可接收来自上皮细胞、基质细胞、神经细胞和其他免疫细胞的信号，进而调控下游效应细胞的功能，从而在肺、皮肤等屏障组织发挥重要的效应功能。本文将对ILC2s的分类、发育和主要功能进行概括，对近年来ILC2s的主要研究进展作一综述。

关键词:Ⅱ型固有淋巴细胞,哮喘,肿瘤,代谢

Xinyue XU, Xiuli JING, Hua TANG. Research progress of type Ⅱ innate lymphocytes[J]. Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences, 2022, 43(9): 666-673.

徐心悦, 景秀丽, 唐华. Ⅱ型固有淋巴细胞的研究进展[J]. betway必威登陆网址（betway.com ）学报, 2022, 43(9): 666-673.

References94

1	Orimo K， Tamari M， Saito H， et al. Characteristics of tissue-resident ILCs and their potential as therapeutic targets in mucosal and skin inflammatory diseases［J］. Allergy， 2021， 76（11）： 3332.
2	Meininger I， Carrasco A， Rao A， et al. Tissue-specific features of innate lymphoid cells［J］. Trends Immunol， 2020， 41（10）： 902.
3	Vivier E， Artis D， Colonna M， et al. Innate lymphoid cells： 10 years on［J］. Cell， 2018， 174（5）： 1054.
4	Roan F， Obata-Ninomiya K， Ziegler SF. Epithelial cell-derived cytokines： more than just signaling the alarm［J］. J Clin Invest， 2019， 129（4）： 1441.
5	Romera-Hernández M， Mathä L， Steer CA， et al. Identification of group 2 innate lymphoid cells in mouse lung， liver， small intestine， bone marrow， and mediastinal and mesenteric lymph nodes［J］. Curr Protoc Immunol， 2019， 125（1）： e73.
6	Kim DH， Van Dyken SJ. ILC2s in high definition： decoding the logic of tissue-based immunity［J］. Trends Immunol， 2020， 41（1）： 7.
7	Olguín-Martínez E， Ruiz-Medina BE， Licona-Limón P. Tissue-specific molecular markers and heterogeneity in type 2 innate lymphoid cells［J］. Front Immunol， 2021， 12： 757967.
8	Guia S， Narni-Mancinelli E. Helper-like innate lymphoid cells in humans and mice［J］. Trends Immunol， 2020， 41（5）： 436.
9	Mjösberg JM， Trifari S， Crellin NK， et al. Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161［J］. Nat Immunol， 2011， 12（11）： 1055.
10	Liu SC， Sirohi K， Verma M， et al. Optimal identification of human conventional and nonconventional （CRTH2^-IL7Rα^-） ILC2s using additional surface markers［J］. J Allergy Clin Immunol， 2020， 146（2）： 390.
11	Zhu JF. T helper 2 （Th2） cell differentiation， type 2 innate lymphoid cell （ILC2） development and regulation of interleukin-4 （IL-4） and IL-13 production［J］. Cytokine， 2015， 75（1）： 14.
12	Kondo M. Lymphoid and myeloid lineage commitment in multipotent hematopoietic progenitors［J］. Immunol Rev， 2010， 238（1）： 37.
13	Ghaedi M， Steer CA， Martinez-Gonzalez I， et al. Common-lymphoid-progenitor-independent pathways of innate and T lymphocyte development［J］. Cell Rep， 2016， 15（3）： 471.
14	Harly C， Kenney D， Ren G， et al. The transcription factor TCF-1 enforces commitment to the innate lymphoid cell lineage［J］. Nat Immunol， 2019， 20（9）： 1150.
15	Yu XF， Wang YH， Deng M， et al. The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor［J］. Elife， 2014， 3： e04406.
16	Zhong C， Zheng MZ， Cui KR， et al. Differential expression of the transcription factor GATA3 specifies lineage and functions of innate lymphoid cells［J］. Immunity， 2020， 52（1）： 83.
17	Yu Y， Tsang JC， Wang C， et al. Single-cell RNA-seq identifies a PD-1^hiILC progenitor and defines its development pathway［J］. Nature， 2016， 539（7627）： 102.
18	Xu W， Cherrier DE， Chea S， et al. An Id2^RFP-reporter mouse redefines innate lymphoid cell precursor potentials［J］. Immunity， 2019， 50（4）： 1054.
19	Liu C， Gong YD， Zhang H， et al. Delineating spatiotemporal and hierarchical development of human fetal innate lymphoid cells［J］. Cell Res， 2021， 31（10）： 1106.
20	Schneider C， Lee J， Koga S， et al. Tissue-resident group 2 innate lymphoid cells differentiate by layered ontogeny and in situ perinatal priming［J］. Immunity， 2019， 50（6）： 1425.
21	Koga S， Hozumi K， Hirano KI， et al. Peripheral PDGFRα⁺gp38⁺mesenchymal cells support the differentiation of fetal liver-derived ILC2［J］. J Exp Med， 2018， 215（6）： 1609.
22	Ghaedi M， Shen ZY， Orangi M， et al. Single-cell analysis of RORα tracer mouse lung reveals ILC progenitors and effector ILC2 subsets［J］. J Exp Med， 2020， 217（3）： jem.20182293.
23	Zeis P， Lian M， Fan XY， et al. In situ maturation and tissue adaptation of type 2 innate lymphoid cell progenitors［J］. Immunity， 2020， 53（4）： 775.
24	Shin SB， Lo BC， Ghaedi M， et al. Abortive γδTCR rearrangements suggest ILC2s are derived from T-cell precursors［J］. Blood Adv， 2020， 4（21）： 5362.
25	Ferreira ACF， Szeto ACH， Heycock MWD， et al. RORα is a critical checkpoint for T cell and ILC2 commitment in the embryonic thymus［J］. Nat Immunol， 2021， 22（2）： 166.
26	Seehus CR， Aliahmad P， De La Torre B， et al. The development of innate lymphoid cells requires TOX-dependent generation of a common innate lymphoid cell progenitor［J］. Nat Immunol， 2015， 16（6）： 599.
27	Yang Q， Li FY， Harly C， et al. TCF-1 upregulation identifies early innate lymphoid progenitors in the bone marrow［J］. Nat Immunol， 2015， 16（10）： 1044.
28	Lei AH， Xiao Q， Liu GY， et al. ICAM-1 controls development and function of ILC2［J］. J Exp Med， 2018， 215（8）： 2157.
29	Zhong C， Zhu JF. Transcriptional regulators dictate innate lymphoid cell fates［J］. Protein Cell， 2017， 8（4）： 242.
30	Zhong C， Zhu JF. Bcl11b drives the birth of ILC2 innate lymphocytes［J］. J Exp Med， 2015， 212（6）： 828.
31	Walker JA， Clark PA， Crisp A， et al. Polychromic reporter mice reveal unappreciated innate lymphoid cell progenitor heterogeneity and elusive ILC3 progenitors in bone marrow［J］. Immunity， 2019， 51（1）： 104.
32	Wang L， Tang J， Yang X， et al. TGF-β induces ST2 and programs ILC2 development［J］. Nat Commun， 2020， 11（1）： 35.
33	Li Q， Li DL， Zhang X， et al. E3 ligase VHL promotes group 2 innate lymphoid cell maturation and function via glycolysis inhibition and induction of interleukin-33 receptor［J］. Immunity， 2018， 48（2）： 258.
34	Miller MM， Reinhardt RL. The heterogeneity， origins， and impact of migratory iILC2 cells in anti-helminth immunity［J］. Front Immunol， 2020， 11： 1594.
35	Huang YF， Guo LY， Qiu J， et al. IL-25-responsive， lineage-negative KLRG1^hicells are multipotential 'inflammatory' type 2 innate lymphoid cells［J］. Nat Immunol， 2015， 16（2）： 161.
36	Flamar AL， Klose CSN， Moeller JB， et al. Interleukin-33 induces the enzyme tryptophan hydroxylase 1 to promote inflammatory group 2 innate lymphoid cell-mediated immunity［J］. Immunity， 2020， 52（4）： 606.
37	Miller MM， Patel PS， Bao K， et al. BATF acts as an essential regulator of IL-25-responsive migratory ILC2 cell fate and function［J］. Sci Immunol， 2020， 5（43）： eaay3994.
38	Ricardo-Gonzalez RR， Schneider C， Liao C， et al. Tissue-specific pathways extrude activated ILC2s to disseminate type 2 immunity［J］. J Exp Med， 2020， 217（4）： e20191172.
39	Huang YF， Mao KR， Chen X， et al. S1P-dependent interorgan trafficking of group 2 innate lymphoid cells supports host defense［J］. Science， 2018， 359（6371）： 114.
40	Halim TY， Steer CA， Mathä L， et al. Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation［J］. Immunity， 2014， 40（3）： 425.
41	Monticelli LA， Buck MD， Flamar AL， et al. Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation［J］. Nat Immunol， 2016， 17（6）： 656.
42	Van Der Ploeg EK， Golebski K， Van Nimwegen M， et al. Steroid-resistant human inflammatory ILC2s are marked by CD45RO and elevated in type 2 respiratory diseases［J］. Sci Immunol， 2021， 6（55）： eabd3489.
43	Seehus CR， Kadavallore A， Torre B， et al. Alternative activation generates IL-10 producing type 2 innate lymphoid cells［J］. Nat Commun， 2017， 8（1）： 1900.
44	Miyamoto C， Kojo S， Yamashita M， et al. Runx/Cbfβ complexes protect group 2 innate lymphoid cells from exhausted-like hyporesponsiveness during allergic airway inflammation［J］. Nat Commun， 2019， 10（1）： 447.
45	Howard E， Lewis G， Galle-Treger L， et al. IL-10 production by ILC2s requires Blimp-1 and cMaf， modulates cellular metabolism， and ameliorates airway hyperreactivity［J］. J Allergy Clin Immunol， 2021， 147（4）： 1281.
46	Golebski K， Layhadi JA， Sahiner U， et al. Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response［J］. Immunity， 2021， 54（2）： 291.
47	Hochdörfer T， Winkler C， Pardali K， et al. Expression of c-Kit discriminates between two functionally distinct subsets of human type 2 innate lymphoid cells［J］. Eur J Immunol， 2019， 49（6）： 884.
48	Scadding GK， Scadding GW. Innate and adaptive immunity： ILC2 and Th2 cells in upper and lower airway allergic diseases［J］. J Allergy Clin Immunol Pract， 2021， 9（5）： 1851.
49	Gauvreau GM， Sehmi R， Ambrose CS， et al. Thymic stromal lymphopoietin： its role and potential as a therapeutic target in asthma［J］. Expert Opin Ther Targets， 2020， 24（8）： 777.
50	Borowczyk J， Shutova M， Brembilla NC， et al. IL-25 （IL-17E） in epithelial immunology and pathophysiology［J］. J Allergy Clin Immunol， 2021， 148（1）： 40.
51	Portelli MA， Hodge E， Sayers I. Genetic risk factors for the development of allergic disease identified by genome-wide association［J］. Clin Exp Allergy， 2015， 45（1）： 21.
52	Boberg E， Johansson K， Malmhäll C， et al. Interplay between the IL-33/ST2 axis and bone marrow ILC2s in protease allergen-induced IL-5-dependent eosinophilia［J］. Front Immunol， 2020， 11： 1058.
53	Xu H， Xu J， Xu L， et al. Interleukin-33 contributes to ILC2 activation and early inflammation-associated lung injury during abdominal sepsis［J］. Immunol Cell Biol， 2018， 96（9）： 935.
54	Liu GY， Chen YY， Wang Y， et al. Angiotensin II enhances group 2 innate lymphoid cell responses via AT1a during airway inflammation［J］. J Exp Med， 2022， 219（3）： e20211001.
55	He J， Yang Q， Xiao Q， et al. IRF-7 is a critical regulator of type 2 innate lymphoid cells in allergic airway inflammation［J］. Cell Rep， 2019， 29（9）： 2718.
56	Helou DG， Shafiei-Jahani P， Hurrell BP， et al. LAIR-1 acts as an immune checkpoint on activated ILC2s and regulates the induction of airway hyperreactivity［J］. J Allergy Clin Immunol， 2022， 149（1）： 223.
57	Matsushita K， Tanaka H， Yasuda K， et al. Regnase-1 degradation is crucial for IL-33- and IL-25-mediated ILC2 activation［J］. JCI Insight， 2020， 5（4）： e131480.
58	He J， Jiang GM， Li X， et al. Bilirubin represents a negative regulator of ILC2 in allergic airway inflammation［J］. Mucosal Immunol， 2022， 15（2）： 314.
59	Xiao Q， Han X， Liu GY， et al. Adenosine restrains ILC2-driven allergic airway inflammation via A2A receptor［J］. Mucosal Immunol， 2022， 15（2）： 338.
60	Cao YJ， He YM， Wang XY， et al. Polymorphonuclear myeloid-derived suppressor cells attenuate allergic airway inflammation by negatively regulating group 2 innate lymphoid cells［J］. Immunology， 2019， 156（4）： 402.
61	Maric J， Ravindran A， Mazzurana L， et al. Cytokine-induced endogenous production of prostaglandin D₂is essential for human group 2 innate lymphoid cell activation［J］. J Allergy Clin Immunol， 2019， 143（6）： 2202.
62	Lund SJ， Portillo A， Cavagnero K， et al. Leukotriene C4 potentiates IL-33-Induced group 2 innate lymphoid cell activation and lung inflammation［J］. J Immunol， 2017， 199（3）： 1096.
63	Von Moltke J， O'Leary CE， Barrett NA， et al. Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s［J］. J Exp Med， 2017， 214（1）： 27.
64	Cai T， Qiu JX， Ji Y， et al. IL-17-producing ST2⁺group 2 innate lymphoid cells play a pathogenic role in lung inflammation［J］. J Allergy Clin Immunol， 2019， 143（1）： 229.
65	Maric J， Ravindran A， Mazzurana L， et al. Prostaglandin E₂suppresses human group 2 innate lymphoid cell function［J］. J Allergy Clin Immunol， 2018， 141（5）： 1761.
66	Zhou WS， Zhang J， Toki S， et al. COX inhibition increasesAlternaria-induced pulmonary group 2 innate lymphoid cell responses and IL-33 release in mice［J］. J Immunol， 2020， 205（4）： 1157.
67	Choi Y， Kim YM， Lee HR， et al. Eosinophil extracellular traps activate type 2 innate lymphoid cells through stimulating airway epithelium in severe asthma［J］. Allergy， 2020， 75（1）： 95.
68	Yu QN， Guo YB， Li X， et al. ILC2 frequency and activity are inhibited by glucocorticoid treatment via STAT pathway in patients with asthma［J］. Allergy， 2018， 73（9）： 1860.
69	Machida K， Aw M， Salter BMA， et al. The role of the TL1A/Dr3 axis in the activation of group 2 innate lymphoid cells in subjects with eosinophilic asthma［J］. Am J Respir Crit Care Med， 2020， 202（8）： 1105.
70	Chen RC， Smith SG， Salter B， et al. Allergen-induced Increases in sputum levels of group 2 innate lymphoid cells in subjects with asthma［J］. Am J Respir Crit Care Med， 2017， 196（6）： 700.
71	Christianson CA， Goplen NP， Zafar I， et al. Persistence of asthma requires multiple feedback circuits involving type 2 innate lymphoid cells and IL-33［J］. J Allergy Clin Immunol， 2015， 136（1）： 59.
72	Winkler C， Hochdörfer T， Israelsson E， et al. Activation of group 2 innate lymphoid cells after allergen challenge in asthmatic patients［J］. J Allergy Clin Immunol， 2019， 144（1）： 61.
73	Dhariwal J， Cameron A， Wong E， et al. Pulmonary innate lymphoid cell responses during rhinovirus-induced asthma exacerbationsin vivo： a clinical trial［J］. Am J Respir Crit Care Med， 2021， 204（11）： 1259.
74	Schuijs MJ， Png S， Richard AC， et al. ILC2-driven innate immune checkpoint mechanism antagonizes NK cell antimetastatic function in the lung［J］. Nat Immunol， 2020， 21（9）： 998.
75	Saranchova I， Han J， Zaman R， et al. Type 2 innate lymphocytes actuate immunity against tumours and limit cancer metastasis［J］. Sci Rep， 2018， 8（1）： 2924.
76	Kim J， Kim W， Moon UJ， et al. Intratumorally establishing type 2 innate lymphoid cells blocks tumor growth［J］. J Immunol， 2016， 196（5）： 2410.
77	Jacquelot N， Seillet C， Wang MY， et al. Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma［J］. Nat Immunol， 2021， 22（7）： 851.
78	Wang S， Qu Y， Xia PY， et al. Transdifferentiation of tumor infiltrating innate lymphoid cells during progression of colorectal cancer［J］. Cell Res， 2020， 30（7）： 610.
79	Moral JA， Leung J， Rojas LA， et al. ILC2s amplify PD-1 blockade by activating tissue-specific cancer immunity［J］. Nature， 2020， 579（7797）： 130.
80	Wagner M， Ealey KN， Tetsu H， et al. Tumor-derived lactic acid contributes to the paucity of intratumoral ILC2s［J］. Cell Rep， 2020， 30（8）： 2743.
81	Qi JJ， Crinier A， Escalière B， et al. Single-cell transcriptomic landscape reveals tumor specific innate lymphoid cells associated with colorectal cancer progression［J］. Cell Rep Med， 2021， 2（8）： 100353.
82	Galle-Treger L， Hurrell BP， Lewis G， et al. Autophagy is critical for group 2 innate lymphoid cell metabolic homeostasis and effector function［J］. J Allergy Clin Immunol， 2020， 145（2）： 502.
83	Wilhelm C， Harrison OJ， Schmitt V， et al. Critical role of fatty acid metabolism in ILC2-mediated barrier protection during malnutrition and helminth infection［J］. J Exp Med， 2016， 213（8）： 1409.
84	Spencer SP， Wilhelm C， Yang Q， et al. Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity［J］. Science， 2014， 343（6169）： 432.
85	Batyrova B， Luwaert F， Maravelia P， et al. PD-1 expression affects cytokine production by ILC2 and is influenced by peroxisome proliferator-activated receptor-γ［J］. Immun Inflamm Dis， 2020， 8（1）： 8.
86	Helou DG， Shafiei-Jahani P， Lo R， et al. PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity［J］. Nat Commun， 2020， 11（1）： 3998.
87	Karagiannis F， Masouleh SK， Wunderling K， et al. Lipid-droplet formation drives pathogenic group 2 innate lymphoid cells in airway inflammation［J］. Immunity， 2020， 52（5）： 885.
88	Xiao Q， He J， Lei AH， et al. PPARγ enhances ILC2 function during allergic airway inflammation via transcription regulation of ST2［J］. Mucosal Immunol， 2021， 14（2）： 468.
89	Fali T， Aychek T， Ferhat M， et al. Metabolic regulation by PPARγ is required for IL-33-mediated activation of ILC2s in lung and adipose tissue［J］. Mucosal Immunol， 2021， 14（3）： 585.
90	Ercolano G， Gomez-Cadena A， Dumauthioz N， et al. PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions［J］. Nat Commun， 2021， 12（1）： 2538.
91	Lewis G， Wang BW， Shafiei Jahani P， et al. Dietary fiber-induced microbial short chain fatty acids suppress ILC2-dependent airway inflammation［J］. Front Immunol， 2019， 10： 2051.
92	Fu LH， Zhao J， Huang JY， et al. A mitochondrial STAT3-methionine metabolism axis promotes ILC2-driven allergic lung inflammation［J］. J Allergy Clin Immunol， 2022， 149（6）： 2091.
93	Okamura T， Hashimoto Y， Mori J， et al. ILC2s improve glucose metabolism through the control of saturated fatty acid absorption within visceral fat［J］. Front Immunol， 2021， 12： 669629.
94	Wang L， Luo Y， Luo LP， et al. Adiponectin restrains ILC2 activation by AMPK-mediated feedback inhibition of IL-33 signaling［J］. J Exp Med， 2021， 218（2）： e20191054.

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