Research progress in the role of typeⅡinnate lymphoid cells and their upstream molecules in the pathogenesis of allergic conjunctivitis

doi:10.3877/cma.j.issn.2095-2007.2024.06.009

Abstract

Abstract:

Allergic conjunctivitis（AC）is a common allergic disease of the human ocular surface whose pathogenesis is complex and is primarily thought to be an immune response mediated by immunoglobulin E（IgE）or T lymphocytes.Currently，one of the main pathogenic mechanisms of allergic inflammation is thought to be the T helper cell（Th2）-dominated hypersensitivity reaction，but little is known about other upstream channels of allergy.Emerging studies have revealed new cellular and molecular mechanisms by which the epithelium activates typeⅡinnate lymphoid cell（ILC2）through the production of pro-allergic cytokines，eg.interleukin（IL）-33，thymic stromal lymphopoietin（TSLP），etc.that in turn modulate the Th2 response.Furthermore，it was concluded that the type 2 immune response driven by ocular surface innate immunity is dependent on the involvement of IL-33，TSLP，basophils，and ILC2 in a mouse model of conjunctivitis induced by papain-impregnated contact lenses.At present，the mechanism of action of ILC2 and epithelial pro-allergic cytokines（IL-33，TSLP，etc.）in the pathogenesis of AC has not been fully elucidated.Therefore，the current status of research on ILC2 and their upstream molecules in the pathogenesis of allergic conjunctivitis was reviewed in this paper.

Key words: Allergic, Conjunctivitis, T helper cell, Innate lymphoid cell 2, Interleukin-33, Thymic stromal lymphhopoietin

Qi Liu, Xiaofen Zheng. Research progress in the role of typeⅡinnate lymphoid cells and their upstream molecules in the pathogenesis of allergic conjunctivitis[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2024, 14(06): 368-374.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhykyxzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-2007.2024.06.009

https://zhykyxzz.cma-cmc.com.cn/EN/Y2024/V14/I06/368

Figures/Tables 1

References 70

［1］	中华医学会眼科学分会角膜病学组.我国过敏性结膜炎诊断和治疗专家共识（2018年）［J］.中华眼科杂志，2018，54（6）：409-414.
［2］	Thong BYH.Allergic conjunctivitis in Asia［J］.Asia Pac Allergy，2017，7（2）：57-64.
［3］	Leonardi A，Silva D，Perez-Formigo D，et al.Management of ocular allergy［J］.Allergy，2019，74（9）：1611-1630.
［4］	Michailopoulos P，Almaliotis D，Georgiadou I，et al.Allergic conjunctivitis in patients with respiratory allergic symptoms；a retrospective study in Greece［J］.Medical Hypothesis，Discovery and Innovation in Ophthalmology，2017，6（1）：3-9.
［5］	陈家利，周华祥，蒋怡，等.过敏性结膜炎中西医治疗进展［J］.中国中医眼科杂志，2020，30（5）：375-378.
［6］	Bielory L，Delgado L，Katelaris CH，et al.ICON：diagnosis and management of allergic conjunctivitis［J］.Ann Allerg Asthma Im，2020，124（2）：118-134.
［7］	Elieh-Ali-Komi D，Rambasek T，Bielory L.Clinical implications of mast cell involvement in allergic conjunctivitis［J］.Allergy，2018，73（3）：528-539.
［8］	宁婵慧，李冰，郑晓汾.T细胞及其细胞因子在过敏性结膜炎作用机制的研究［J］.国际眼科纵览，2015，39（5）：357-360.
［9］	León B，Ballesteros-Tato A.Modulating Th2 cell immunity for the treatment of asthma［J］.Front Immunol，2021，12：637948.
［10］	Iwasaki N，Terawaki S，Shimizu K，et al.Th2 cells and macrophages cooperatively induce allergic inflammation through histamine signaling［J］.Plos One，2021，16（3）：e0248158.
［11］	Shin S，Lee J H，Lee H J，et al.Rapamycin attenuates Th2-driven experimental allergic conjunctivitis［J］.Clin Immunol，2018，190：1-10.
［12］	王静静，宋昕阳，钱友存.白介素-17家族细胞因子的研究进展［J］.生命科学，2016，28（2）：170-181.
［13］	Meng XT，Shi YY，Zhang H，et al.The role of Th17 cells and IL-17 in Th2 immune responses of allergic conjunctivitis［J］.J Ophthalmol，2020：6917185.
［14］	Kinyanjui MW，Shan J，Nakada EM，et al.Dose-dependent effects of IL-17 on IL-13-induced airway inflammatory responses and airway hyperresponsiveness［J］.JImmunol，2013，190（8）：3859-3868.
［15］	Bai MT，Li Y， Hu ZL.Ragweed pollen induces allergic conjunctivitis immunetolerancein mice via regulation of the NF-κB signal pathway［J］.Int J Ophthalmol，2021，14（7）：955-964.
［16］	Chen X，Deng R，Chi W，et al.IL-27 signaling deficiency develops Th17-enhanced Th2-dominant inflammation in murine allergic conjunctivitis model［J］.Allergy，2019，74（5）：910-921.
［17］	Wan X，Zhang Y，Tang H，et al.IL-27 signaling negatively regulates FcζRI-mediated mast cell activation and allergic response［J］.JLeukocyte Biol，2022，112（3）：411-424.
［18］	Kemter AM，Nagler CR.Influences on allergic mechanisms through gut，lung，and skin microbiome exposures［J］.J Clin Invest，2019，129（4）：1483-1492.
［19］	Liang Q，Li J，Zhang S，et al.Characterization of conjunctival microbiome dysbiosis associated with allergic conjunctivitis［J］.Authorea Preprints，2020，76（2）：596-600.
［20］	Zarzuela JC，Reinoso R，Armentia A，et al.Conjunctival intraepithelial lymphocytes， lacrimal cytokines and ocular commensal microbiota：analysis of the three main players in allergic conjunctivitis［J］.Front Immunol，2022，13：911022.
［21］	Zeissig S，Blumberg RS.Commensal microbiota and NKT cells in the control of inflammatory diseases at mucosal surfaces［J］.Curr Opin Immunol，2013，25（6）：690-696.
［22］	Ivanov II，de Llanos Frutos R，Manel N，et al.Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine［J］.Cell Host Microbe，2008，4（4）：337-349.
［23］	Knoop KA，Newberry RD.Goblet cells：multifaceted players in immunity at mucosal surfaces［J］.Mucosal Immunol，2018，11（6）：1551-1557.
［24］	Portal C，Gouyer V，Gottrand F，et al.Ocular mucins in dry eye disease［J］.Exp Eye Res，2019，186：107724.
［25］	Hodges RR，Dartt DA.Tear film mucins：front line defenders of the ocular surface；comparison with airway and gastrointestinal tract mucins［J］.Exp Eye Res，2013，117：62-78.
［26］	Birchenough GMH，Nyström EEL，Johansson MEV，et al.A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion［J］.Science，2016，352（6293）：1535-1542.
［27］	Wlodarska M，Thaiss CA，Nowarski R，et al.NLRP6 inflammasome orchestrates thecolonic host-microbial interfaceby regulatinggoblet cell mucus secretion［J］.Cell，2014，156（5）：1045-1059.
［28］	Ermund A，Schütte A，Johansson MEV，et al.Studies of mucus in mouse stomach，small intestine，and colon.I.Gastrointestinal mucus layers have different properties depending on location as well as over the Peyer's patches［J］.Am J Physiol-Gastr L，2013，305（5）：G341-G347.
［29］	García-Posadas L，Hodges RR，Diebold Y，et al.Contextdependent regulation of conjunctival goblet cell function by allergic mediators［J］.Sci Rep，2018，8（1）：12162.
［30］	Matsuzawa M，Ando T，Fukase S，et al.The protective role of conjunctival goblet cell mucin sialylation［J］.Nat Commun，2023，14（1）：1417.
［31］	Singh N，Diebold Y，Sahu SK，et al.Epithelial barrier dysfunction in ocular allergy［J］.Allergy，2022，77（5）：1360-1372.
［32］	Cayrol C，Girard JP.IL-33：an alarmin cytokine with crucial roles in innate immunity，inflammation and allergy［J］.Curr Opin Immunol，2014，31：31-37.
［33］	Schmitz J，Owyang A，Oldham E，et al.IL-33，an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines［J］.Immunity，2005，23（5）：479-490.
［34］	Pichery M，Mirey E，Mercier P，et al.Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues，lymphoid organs，brain，embryos，and inflamed tissues：in situ analysis using a novel Il-33-LacZ gene trap reporter strain［J］.J Immunol，2012，188（7）：3488-3495.
［35］	Liew FY，Pitman NI，McInnes IB.Disease-associated functions of IL-33：the new kid in the IL-1 family［J］.Nat Rev Immunol，2010，10（2）：103-110.
［36］	Yasuoka S，Kawanokuchi J，Parajuli B，et al.Production and functions of IL-33 in the central nervous system［J］.Brain Res，2011，1385：8-17.
［37］	Dwyer GK，D'Cruz LM，Turnquist HR.Emerging functions of IL-33 in homeostasis and immunity［J］.Annu Rev Immunol，2022，40（1）：15-43.
［38］	Hu J，Gao N，Zhang Y，et al.IL-33/ST2/IL-9/IL-9R signaling disrupts ocular surface barrier in allergic inflammation［J］.Mucosal Immunol，2020，13（6）：919-930.
［39］	Huang CC，Yang W，Guo C，et al.Anatomical and functional dichotomy of ocular itch and pain［J］.Nat Med，2018，24（8）：1268-1276.
［40］	Oetjen LK，Mack MR，Feng J，et al.Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch［J］.Cell，2017，171（1）：217-228.
［41］	Liu B，Tai Y，Achanta S，et al.IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy［J］.Proceedings of the National Academy of Sciences，2016，113（47）：E7572-E7579.
［42］	Okano M，Hirahara K，Kiuchi M，et al.Interleukin-33-activated neuropeptide CGRP-producing memory Th2 cells cooperate with somatosensory neurons to induce conjunctival itch［J］.Immunity，2022，55（12）：2352-2368.
［43］	Koyasu S，Moro K.Innate Th2-type immune responses and the natural helper cell，a newly identified lymphocyte population［J］.Curr Opin Allergy Cl，2011，11（2）：109-114.
［44］	姚娟，郑晓汾，李冰.胸腺基质淋巴细胞生成素在过敏性结膜炎发病中的作用［J］.国际眼科纵览，2015，39（3）：190-194.
［45］	Kim B，Kim TH.Fundamental role of dendritic cells in inducing Th2 responses［J］.Korean J Intern Med，2018，33（3）：483-489.
［46］	Fallon PG，Ballantyne SJ，Mangan NE，et al.Identification of an interleukin（IL）-25-dependent cell population that provides IL-4，IL-5，and IL-13 at the onset of helminth expulsion［J］.J Exp Med，2006，203（4）：1105-1116.
［47］	Roediger B，Kyle R，Tay SS，et al.IL-2 is a critical regulator of group 2 innate lymphoid cell function during pulmonary inflammation［J］.JAllergy Clin Immun，2015，136（6）：1653-1663.e7.
［48］	Drake LY，Iijima K，Kita H.Group 2 innate lymphoid cells and CD 4⁺T cells cooperate to mediate type 2 immune response in mice［J］.Allergy，2014，69（10）：1300-1307.
［49］	Oliphant CJ，Hwang YY，Walker JA，et al.MHCII-mediated dialog between group 2 innate lymphoid cells and CD4⁺T cells potentiates type 2 immunity and promotes parasitic helminth expulsion［J］.Immunity，2014，41（2）：283-295.
［50］	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）：8-23.
［51］	Jenkins SJ，Perona-Wright G，Worsley AGF，et al.Dendritic cell expression of OX40 ligand acts as a costimulatory，not polarizing，signal for optimal Th2 priming and memory induction in vivo［J］.JImmunol，2007，179（6）：3515-3523.
［52］	Mortha A， Burrows K.Cytokine networks between innate lymphoid cells and myeloid cells［J］.Front Immunol，2018，9：191.
［53］	Halim TYF，Steer CA，MathäL，et al.Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cellmediated allergic lung inflammation［J］.Immunity，2014，40（3）：425-435.
［54］	Mortaz E，Amani S，Mumby S，et al.Role of mast cells and type 2 innate lymphoid（ILC2）cells in lung transplantation［J］.J Immunol Res，2018：2785971.
［55］	Kim BS，Wang K，Siracusa MC，et al.Basophils promote innate lymphoid cell responses in inflamed skin［J］.J Immunol，2014，193（7）：3717-3725.
［56］	Barlow JL，Peel S，Fox J，et al.IL-33 is more potent than IL-25 in provoking IL-13-producing nuocytes（type 2 innate lymphoid cells）and airway contraction［J］.J Allergy Clin Immun，2013，132（4）：933-941.
［57］	Imai Y.Interleukin-33 in atopic dermatitis［J］.J Dermatol Sci，2019，96（1）：2-7.
［58］	Corrigan CJ，Wang W，Meng Q，et al.Allergen-induced expression of IL-25 and IL-25 receptor in atopic asthmatic airways and late-phase cutaneous responses［J］.J Allergy Clin Immun，2011，128（1）：116-124.
［59］	Wang YH，Angkasekwinai P，Lu N，et al.IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells［J］.J Exp Med，2007，204（8）：1837-1847.
［60］	Cayrol C，Girard JP.Interleukin-33（IL-33）：a nuclear cytokine from the IL-1 family［J］.Immunol Rev，2018，281（1）：154-168.
［61］	Molofsky AB，Savage AK，Locksley RM.Interleukin-33 in tissue homeostasis，injury，and inflammation［J］.Immunity，2015，42（6）：1005-1019.
［62］	Liew FY，Girard JP，Turnquist HR.Interleukin-33 in health and disease［J］.Nat Rev Immunol，2016，16（11）：676-689.
［63］	Morita H，Moro K，Koyasu S.Innate lymphoid cells in allergic and nonallergic inflammation［J］.J Allergy Clin Immun，2016，138（5）：1253-1264.
［64］	Topczewska PM，Rompe ZA，Jakob MO，et al.ILC2 require cell-intrinsic ST2 signals to promote type 2 immune responses［J］.Front Immunol，2023，14：1130933.
［65］	Salimi M，Stöger L，Liu W，et al.Cysteinyl leukotriene E4 activates human group 2 innate lymphoid cells and enhances the effect of prostaglandin D2 and epithelial cytokines［J］.J Allergy Clin Immun，2017，140（4）：1090-1100.
［66］	Kim BS，Siracusa MC，Saenz SA，et al.TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation［J］.Sci Transl Med，2013，5（170）：170ra16.
［67］	Salimi M，Barlow JL，Saunders SP，et al.A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis［J］.J Exp Med，2013，210（13）：2939-2950.
［68］	Liu Z，Yang X，Liu X，et al.Analysis of expression of ILC2 cells in nasal mucosa based on animal model of allergic bacterial infection rhinitis［J］.J Infect Public Heal，2021，14（1）：77-83.
［69］	Chen R，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 Resp Crit Care，2017，196（6）：700-712.
［70］	Sugita J，Asada Y，Ishida W，et al.Contributions of Interleukin-33 and TSLP in a papain-soaked contact lens-induced mouse conjunctival inflammation model［J］.Immun Inflamm Dis，2017，5（4）：515-525.

[1]	Yahui Sun, Tiantian Li. Mechanism of regulatory T cells/T helper cell 17 imbalance in patients with pancreatic infection secondary to severe acute pancreatitis [J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2023, 16(06): 475-480.
[2]	Qing Liu, Yunchao Wang, Tongyi Men, Huayu Gao, Jianning Wang. A case of acute pancreatitis complicated with pleural effusion and allergic purpura after donation after cardiac death kidney transplantation [J]. Chinese Journal of Transplantation(Electronic Edition), 2021, 15(01): 52-54.
[3]	Dan Wang, Wensi Li, Suhuang Cheng, Ze Ji, Xiang Zhu, Chunyan Hao. Expression of Treg/Th17 and DC cells in different COPD progression stages and their relationships with prognosis [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2024, 17(05): 685-689.
[4]	Li Wang, Xiaojun Wang. TH17 cells balance and mechanism in the immune microenvironment on the pathogenesis of allergic asthma [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2020, 13(05): 648-652.
[5]	zhengwei Fu, Lixia Wang, Haiyan Ge. Effect of mesenchymal stem cells on the balance of Th17/Treg and its relationship with IBD [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2018, 08(06): 373-378.
[6]	Yuan Wei, Xizhan Xu, Qingfeng Liang. Advances in ocular microflora of immune ocular surface diseases [J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2023, 13(01): 55-59.
[7]	Huan Gao, Xiaofen Zheng. The role of M2 macrophage polarization in the pathogenesis of allergic conjunctivitis involving TSLP and its downstream molecules [J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2022, 12(04): 232-236.
[8]	Hong Chen, Weiwei Zhang, Dan Wu, Liang Gao. Effects of seasonal allergic conjunctivitis on ocular surface in diabetes mellitus patients [J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2020, 10(04): 206-211.
[9]	Pengfei Yu, Xingjin Mai, Shuqiang Fu, Baoshou Su, Yimin Wu, Wenqing Yu. Value of serum levels of sTREM-1, IL-12 and IL-33 in evaluating the severity and prognosis of traumatic brain injury [J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2022, 08(01): 18-22.
[10]	Jun Dai, Shuo Li, Ying Cao, Shoufeng Wang, Hongmao Song, Jingjing Cai, Min Shao, Li Chen, Lei Cheng, De Huai. Efficacy of modified highly selective pterygoid canal nerve block by low temperature radiofrequency ablation under nasal endoscopy in patients with moderate to severe chronic rhinitis [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(06): 689-693.
[11]	Min Huang, Xuefen Chen, Zhouru Shen, Zhiyi He, Jing Bai, Meihua Li, Meiling Yang, Jingmin Deng. Clinical characteristics of 21 cases of mixed types of pulmonary aspergillosis [J]. Chinese Journal of Clinicians(Electronic Edition), 2022, 16(12): 1217-1223.
[12]	Yuanhui Wu, Youjin Zhu, Xiangzhao Zhou, Jie Wen, Xiaoli Gao, Dongmei Feng. Relationship of serum IL-1β, IL-27 and IL-33 with cellular immune status in patients with early syphilis [J]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(09): 666-671.
[13]	Qiaozhi Qin, Yuehong Tao. Immunomodulatory effects of sublingual immunotherapy on type 2 innate lymphocytes and related cytokine in peripheral blood of children with allergic asthma [J]. Chinese Journal of Clinicians(Electronic Edition), 2018, 12(07): 388-393.
[14]	Weizhong Song, Luyang Lin. Analysis of serum allergen-specific IgE antibodies in patients with allergic skin diseases [J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2023, 11(02): 90-94.
[15]	Xinrui Zeng, Jiamin Liang, Yijie Wang, Yun Chen, Jiaying Luo, Feng Wang, Baoqing Sun. The clinical significance of eosinophil count in patients with allergic rhinitis [J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2021, 09(03): 138-142.

Please choose a citation manager

Content to export