固有免疫和适应性免疫在变应性鼻炎发病中的作用机制
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摘要
<正>变应性鼻炎(allergic rhinitis,AR)是一种常见的上呼吸道慢性炎性疾病,临床表现为喷嚏、清水样涕、鼻塞及鼻痒等症状。AR是全球最常见的过敏性疾病之一,根据有关流行病学调查推算,AR影响着10%～40%的世界人口,我国成人AR患病率为17.6%,并在最近6年显著增加,严重影响患者的健康和生活质量,同时也造成了沉重的医疗和社会负担[1-2]。AR是一个值得重视的免疫系统疾病,
The pathogenesis of allergic rhinitis(AR)has not well been clarified,and the imbalance of immune system is its important feature.Interaction between innate and adaptive immune cells and inflammatory mediators secreted by them triggers,maintains and aggravates AR.In this review,Toll-like receptor signaling pathways are used as a bridge to systematically analyze the mechanisms of innate and adaptive immunity in the development of AR.
The pathogenesis of allergic rhinitis(AR)has not well been clarified,and the imbalance of immune system is its important feature.Interaction between innate and adaptive immune cells and inflammatory mediators secreted by them triggers,maintains and aggravates AR.In this review,Toll-like receptor signaling pathways are used as a bridge to systematically analyze the mechanisms of innate and adaptive immunity in the development of AR.
引文
[1] CHENG L,CHEN J,FU Q,et al.Chinese society of allergy guidelines for diagnosis and treatment of allergic rhinitis[J].Allergy Asthma Immunol Res,2018,10:300-353.
[2] WANG X D,ZHENG M,LOU H F,et al.An increased prevalence of self-reported allergic rhinitis in major Chinese cities from 2005to 2011[J].Allergy,2016,71:1170-1180.
[3] IWASAKI A,MEDZHITOV R.Regulation of adaptive immunity by the innate immune system[J].Science,2010,327:291-295.
[4] EIFAN A O,DURHAM S R.Pathogenesis of rhinitis[J].Clin Exp Allergy,2016,46:1139-1151.
[5] DECKERS J,BRANCO MADEIRA F,HAMMAD H.Innate immune cells in asthma[J].Trends Immunol,2013,34:540-547.
[6] DUNLOP J,MATSUI E,SHARMA H P.Allergic rhinitis:environmental determinants[J].Immunol Allergy Clin North Am,2016,36:367-377.
[7] TOMAZIC P V,BIRNER-GRUENBERGER R,LEITNER A,et al.Nasal mucus proteomic changes reflect altered immune responses and epithelial permeability in patients with allergic rhinitis[J].J Allergy Clin Immunol,2014,133:741-750.
[8] TOMAZIC P V,BIRNER-GRUENBERGER R,LEITNER A,et al.Seasonal proteome changes of nasal mucus reflect perennial inflammatory response and reduced defence mechanisms and plasticity in allergic rhinitis[J].J Proteomics,2016,133:153-160.
[9] LEE H J,KIM B,IM N R,et al.Decreased expression of E-cadherin and ZO-1in the nasal mucosa of patients with allergic rhinitis:altered regulation of Ecadherin by IL-4,IL-5,and TNF-alpha[J].Am J Rhinol Allergy,2016,30:173-178.
[10]SONG J,ZHAO H,DONG H,et al.Mechanism of E-cadherin redistribution in bronchial airway epithelial cells in a TDI-induced asthma model[J].Toxicol Lett,2013,220:8-14.
[11]孟楠楠,侯赟,桂岩,等.甲基丁香酚对变应性鼻炎大鼠鼻黏膜组织中黏蛋白5AC的影响[J].浙江大学学报(医学版),2016,45(5):476-484.
[12]SHAH S A,ISHINAGA H,HOU B,et al.Effects of interleukin-31on MUC5AC gene expression in nasal allergic inflammation[J].Pharmacology,2013,91:158-164.
[13] WANG Y,LV L,ZANG H,et al.Regulation of Trek1expression in nasal mucosa with allergic rhinitis by specific immunotherapy[J].Cell Biochem Funct,2015,33:23-28.
[14]RENKONEN J, TOPPILA-SALMIS, JOENVAARA S,et al.Expression of Toll-like receptors in nasal epithelium in allergic rhinitis[J].Apmis,2015,123:716-725.
[15]MOREIRA A P,CAVASSANI K A,ISMAILOGLU U B,et al.The protective role of TLR6in a mouse model of asthma is mediated by IL-23and IL-17A[J].J Clin Invest,2011,121:4420-4432.
[16]CUI X Y,CHEN X,YU C J,et al.Increased expression of toll-like receptors 2and 4and related cytokines in persistent allergic rhinitis[J].Otolaryngol Head Neck Surg,2015,152:233-238.
[17]FRANSSON M,ADNER M,ERJEFALT J,et al.Up-regulation of Toll-like receptors 2,3and 4in allergic rhinitis[J].Respir Res,2005,6:100-104.
[18]VANHINSBERGH L J,POWE D G,JONES N S.Reduction of TLR2gene expression in allergic and nonallergic rhinitis[J].Ann Allergy Asthma Immunol,2007,99:509-516.
[19] LAURIELLO M, MICERA A, MUZI P,et al.TLR4and TLR9Expression in different phenotypes of rhinitis[J].Int J Otolaryngol,2012,2012:925-926.
[20]RYU J H,YOO J Y,KIM M J,et al.Distinct TLRmediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways[J].J Allergy Clin Immunol,2013,131:549-561.
[21]SAKAMOTO M,ASAHINA R,KAMISHINA H,et al.Transcription of thymic stromal lymphopoietin via Toll-like receptor 2in canine keratinocytes:apossible association of Staphylococcus spp.in the deterioration of allergic inflammation in canine atopic dermatitis[J].Vet Dermatol,2016,27:e46.
[22]LI M,WANG Z N,YANG L F,et al.TLR4antagonist suppresses airway remodeling in asthma by inhibiting the T-helper 2response[J].Exp Ther Med,2017,14:2911-2916.
[23]TYURIN Y A,LISSOVSKAYA S A,FASSAHOV R S,et al.Cytokine profile of patients with allergic rhinitis caused by pollen,mite,and microbial allergen sensitization[J].J Immunol Res,2017,2017:305-317.
[24]KITAJIMA M,LEE H C,NAKAYAMA T,et al.TSLP enhances the function of helper type 2cells[J].Eur J Immunol,2011,4:1862-1871.
[25]FROIDURE A,SHEN C,PILETTE C.Dendritic cells revisited in human allergic rhinitis and asthma[J].Allergy,2016,71:137-148.
[26]SOUMELIS V,RECHE P A,KANZLER H,et al.Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP[J].Nat Immunol,2002,3:673-680.
[27]HAN N R,OH H A,NAM S Y,et al.TSLP induces mast cell development and aggravates allergic reactions through the activation of MDM2and STAT6[J].J Invest Dermatol,2014,134:2521-2530.
[28]AKASAKI S,MATSUSHITA K,KATO Y,et al.Murine allergic rhinitis and nasal Th2activation are mediated via TSLP-and IL-33-signaling pathways[J].Int Immunol,2016,28:65-76.
[29]PILETTE C,JACOBSON M R,RATAJCZAK C,et al.Aberrant dendritic cell function conditions Th2-cell polarization in allergic rhinitis[J].Allergy,2013,68:312-321.
[30]ELDER M J,WEBSTER S J,WILLIAMS D L,et al.TSLP production by dendritic cells is modulated by IL-1beta and components of the endoplasmic reticulum stress response[J].Eur J Immunol,2016,46:455-463.
[31]MELUM G R,FARKAS L,SCHEEL C,et al.A thymic stromal lymphopoietin-responsive dendritic cell subset mediates allergic responses in the upper airway mucosa[J].J Allergy Clin Immunol,2014,134:613-621.
[32]ALDINUCCI A,BONECHI E,MANUELLI C,et al.Histamine regulates actin cytoskeleton in human toll-like receptor 4-activated monocyte-derived dendritic cells tuning CD4+T lymphocyte response[J].J Biol Chem,2016,291:14803-14814.
[33]DOHERTY T A,BROIDE D H.Group 2innate lymphoid cells:new players in human allergic diseases[J].J Investig Allergol Clin Immunol,2015,25:1-11.
[34] MAGGI L,MONTAINI G,MAZZONI A,et al.Human circulating group 2innate lymphoid cells can express CD154and promote IgE production[J].J Allergy Clin Immunol,2017,139:964-976.
[35]FAN D,WANG X,WANG M,et al.Allergen-dependent differences in ILC2sfrequencies in patients with allergic rhinitis[J].Allergy Asthma Immunol Res,2016,8:216-222.
[36]DHARIWAL J,CAMERON A,TRUJILLO-TORRALBO M B,et al.Mucosal Type 2Innate lymphoid cells are a key component of the allergic response to aeroallergen[J].Am J Respir Crit Care Med,2017,195:1586-1596.
[37]SALIMI M,BARLOW J L,SAUNDERS S P,et al.A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis[J].J Exp Med,2013,210:2939-2950.
[38]LOZANO N A,SARANZ R J,LOZANO A,et al.Analysis of nasal cytology in children and adolescents with rhinitis[J].Rev Fac Cien Med Univ Nac Cordoba,2017,74:126-133.
[39]JIAO D,WONG C K,QIU H N,et al.NOD2and TLR2ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation[J].Cell Mol Immunol,2016,13:535-550.
[40]LONG H,LIAO W,WANG L,et al.A player and coordinator:the versatile roles of eosinophils in the immune system[J].Transfus Med Hemother,2016,43:96-108.
[41]SALTER B M A,SMITH S G,MUKHERJEE M,et al.Human bronchial epithelial cell-derived factors from severe asthmatic subjects stimulate eosinophil differentiation[J].Am J Respir Cell Mol Biol,2018,58:99-106.
[42]SCHNEIDER E,THIEBLEMONT N,DE MORAES M L,et al.Basophils:new players in the cytokine network[J].Eur Cytokine Netw,2010,21:142-153.
[43]STEINER M,HAWRANEK T,SCHNEIDER M,et al.Elevated Toll-Like receptor-induced cxcl8secretion in human blood basophils from allergic donors is independent of toll-like receptor expression levels[J].PLoS One,2016,11:e0149275.
[44]SUURMOND J,STOOP J N,RIVELLESE F,et al.Activation of human basophils by combined toll-like receptor-and FcepsilonRI-triggering can promote Th2skewing of naive T helper cells[J].Eur J Immunol,2014,44:386-396.
[45]SHIRAISHI Y,JIA Y,DOMENICO J,et al.Sequential engagement of fcepsilonri on mast cells and basophil histamine H(4)Receptor and fcepsilonri in allergic rhinitis[J].J Immunol,2013,190:539-548.
[46]彭海森,朱新华.肥大细胞在变应性鼻炎发病机制中的应用研究[J].临床耳鼻咽喉头颈外科杂志,2018,32(2):157-160.
[47]TONIATO E,FRYDAS I,ROBUFFO I,et al.Activation and inhibition of adaptive immune response mediated by mast cells[J].J Biol Regul Homeost Agents,2017,31:543-548.
[48]CHO M,LEE J E,LIM H,et al.Fibrinogen cleavage products and Toll-like receptor 4promote the generation of programmed cell death 1ligand 2-positive dendritic cells in allergic asthma[J].J Allergy Clin Immunol,2018,142:530-541.
[49] NAHID M A,BENSO L M,SHIN J D,et al.TLR4,TLR7/8agonist-induced miR-146apromotes macrophage tolerance to MyD88-dependent TLR agonists[J].J Leukoc Biol,2016,100:339-349.
[50]TATANO Y,SHIMIZU T,TOMIOKA H.Unique macrophages different from M1/M2 macrophages inhibit T cell mitogenesis while upregulating Th17polarization[J].Sci Rep,2014,4:41-46.
[51]尹雪,任秀敏,刘春苗,等.变应性鼻炎患者IL-35对于Treg/Th17细胞平衡的调控作用[J].临床耳鼻咽喉头颈外科杂志,2016,30(3):213-216.
[52]SUN R,TANG X Y,YANG Y.Immune imbalance of regulatory T/type 2helper cells in the pathogenesis of allergic rhinitis in children[J].J Laryngol Otol,2016,130:89-94.
[53]朱鲁平,程雷.辅助性T细胞与变态反应性疾病的关系[J].中华临床免疫和变态反应杂志,2009,3(4):285-289.
[54]TANG J,XIAO P,LUO X,et al.Increased IL-22level in allergic rhinitis significantly correlates with clinical severity[J].Am J Rhinol Allergy,2014,28:197-201.
[55]GU Z W,WANG Y X,CAO Z W.Neutralization of interleukin-9ameliorates symptoms of allergic rhinitis by reducing Th2,Th9,and Th17responses and increasing the Treg response in a murine model[J].Oncotarget,2017,8:14314-14324.
[56]WANG X Q,HU G H,KANG H Y,et al.High frequency of T helper type 9cells in Chinese patients with allergic rhinitis[J].Asian Pac J Allergy Immunol,2015,33:301-307.
[57]CHENG S,WANG H,ZHOU H.The role of TLR4on B cell activation and anti-beta2GPI antibody production in the antiphospholipid syndrome[J].J Immunol Res,2016,2016:1719-1720.
[58] KOMAI-KOMA M,JONES L,OGG G S,et al.TLR2is expressed on activated T cells as a costimulatory receptor[J].Proc Natl Acad Sci U S A,2004,101:3029-3034.
[59]WU X Z,ZHOU Q,LIN H,et al.Immune regulation of toll-like receptor 2 Engagement on CD4+T cells in murine models of malignant pleural effusion[J].Am J Respir Cell Mol Biol,2017,56:342-352.
[60]REYNOLDS J M,DONG C.Toll-like receptor regulation of effector T lymphocyte function[J].Trends Immunol,2013,34:511-519.
[61]REYNOLDS J M,PAPPU B P,PENG J,et al.Tolllike receptor 2signaling in CD4+T lymphocytes promotes T helper 17responses and regulates the pathogenesis of autoimmune disease[J].Immunity,2010,32:692-702.
[62]WANG X,FAN X,BI S,et al.Toll-like receptors 2and 4-mediated reciprocal Th17and antibody responses to group a streptococcus infection[J].J Infect Dis,2017,215:644-652.
[63]HOSOKI K,BOLDOGH I,SUR S.Innate responses to pollen allergens[J].Curr Opin Allergy Clin Immunol,2015,15:79-88.
[64]祁雪萍,索利敏,赵长青,等.T细胞免疫球蛋白黏蛋白分子4参与变应性鼻炎发病机制的实验研究[J].中华耳鼻咽喉头颈外科杂志,2014,49(4):283-287.
[65]黄雪琨,杨钦泰,陈玉莲,等.γσT细胞、调节性T细胞、白细胞介素17及转化生长因子β1在变应性鼻炎患者外周血中的表达[J].中华耳鼻咽喉头颈外科杂志,2013,48(7):544-548.
[66]SOGUT A,YILMAZ O,KIRMAZ C,et al.Regulatory-T,T-helper 1,and T-helper 2cell differentiation in nasal mucosa of allergic rhinitis with olive pollen sensitivity[J].Int Arch Allergy Immunol,2012,157:349-353.
[67]SAAD K,ZAHRAN A M,ELSAYH K I,et al.Variation of Regulatory T lymphocytes in the peripheral blood of children with allergic rhinitis[J].Arch Immunol Ther Exp(Warsz),2017,66:307-313.
[68]蔡克敏,李华斌,程雷.Foxp3+调节性T细胞及其与鼻部炎性疾病的关系[J].中华临床免疫和变态反应杂志,2010,4(1):61-69.
[69]COOMES S M,KANNAN Y,PELLY V S,et al.CD4+Th2cells are directly regulated by IL-10during allergic airway inflammation[J].Mucosal Immunol,2016,10:150-161.
[70]PALOMARESO, MARTIN-FONTECHAM,LAUENER R,et al.Regulatory T cells and immune regulation of allergic diseases:roles of IL-10 and TGF-beta[J].Genes Immun,2014,15:511-520.
[71]YOKOTA M,SUZUKI M,NAKAMURA Y,et al.Cytokine modulation by IL-35in mice with allergic rhinitis[J].Am J Rhinol Allergy,2015,29:251-256.
[72]WHITEHEAD G S,WILSON R H,NAKANO K,et al.IL-35 production by inducible costimulator(ICOS)-positive regulatory T cells reverses established IL-17-dependent allergic airways disease[J].J Allergy Clin Immunol,2012,129:207-215.
[73]杨光,郑国玺,张璐瑶,等.IL-17及IL-23在变应性鼻炎及非变应性鼻炎患者血清及鼻腔分泌物中的相关表达及意义[J].临床耳鼻咽喉头颈外科杂志,2015,29(12):1086-1090.
[74]GU Z W,WANG Y X,CAO Z W.Neutralization of interleukin-17suppresses allergic rhinitis symptoms by downregulating Th2and Th17responses and upregulating the Treg response[J].Oncotarget,2017,8:22361-22369.
[75]MAKIHARA S,OKANO M,FUJIWARA T,et al.Local expression of interleukin-17ais correlated with nasal eosinophilia and clinical severity in allergic rhinitis[J].Allergy Rhinol(Providence),2014,5:22-27.
[76]QUAN S H,ZHANG Y L,HAN D H,et al.Contribution of interleukin 17Ato the development and regulation of allergic inflammation in a murine allergic rhinitis model[J].Ann Allergy Asthma Immunol,2012,108:342-350.
[77]丁莲富,陈强,李岚,等.舌下特异性免疫治疗过敏性鼻炎/过敏性哮喘患儿IL-17和IL-35水平的变化及临床疗效[J].中国当代儿科杂志,2014,16(12):1206-1210.
[78]DARDALHON V,AWASTHI A,KWON H,et al.IL-4inhibits TGF-beta-induced Foxp3+T cells and,together with TGF-beta,generates IL-9+IL-10+Foxp3(-)effector T cells[J].Nat Immunol,2008,9:1347-1355.
[79]FROIDURE A,SHEN C,GRAS D,et al.Myeloid dendritic cells are primed in allergic asthma for thymic stromal lymphopoietin-mediated induction of Th2and Th9responses[J].Allergy,2014,69:1068-1076.
[80]PALAGA T.Driving forces of inflammatory diseases:Th9in allergic rhinitis and estrogen in SLE[J].Asian Pac J Allergy Immunol,2015,33:265-266.
[81]WANG X Q,KE X,SHEN Y,et al.Changes in circulating follicular helper T-cells in Chinese patients with allergic rhinitis[J].Acta Otolaryngol,2016,136:199-204.
[82]BALLESTEROS-TATO A,RANDALL T D.Priming of T follicular helper cells by dendritic cells[J].Immunol Cell Biol,2014,92:22-27.
[83]KAMEKURA R,SHIGEHARA K,MIYAJIMA S,et al.Alteration of circulating type 2follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma[J].Clin Immunol,2015,158:204-211.
[84]KIM A S,DOHERTY T A,KARTA M R,et al.Regulatory B cells and T follicular helper cells are reduced in allergic rhinitis[J].J Allergy Clin Immunol,2016,138:1192-1195.
[85]HE J S,NARAYANAN S,SUBRAMANIAM S,et al.Biology of IgE production:IgE cell differentiation and the memory of IgE responses[J].Curr Top Microbiol Immunol,2015,388:1-19.
[86]MATSUSHITA K,YOSHIMOTO T.B cell-intrinsic MyD88signaling is essential for IgE responses in lungs exposed to pollen allergens[J].J Immunol,2014,193:5791-5800.
[2] WANG X D,ZHENG M,LOU H F,et al.An increased prevalence of self-reported allergic rhinitis in major Chinese cities from 2005to 2011[J].Allergy,2016,71:1170-1180.
[3] IWASAKI A,MEDZHITOV R.Regulation of adaptive immunity by the innate immune system[J].Science,2010,327:291-295.
[4] EIFAN A O,DURHAM S R.Pathogenesis of rhinitis[J].Clin Exp Allergy,2016,46:1139-1151.
[5] DECKERS J,BRANCO MADEIRA F,HAMMAD H.Innate immune cells in asthma[J].Trends Immunol,2013,34:540-547.
[6] DUNLOP J,MATSUI E,SHARMA H P.Allergic rhinitis:environmental determinants[J].Immunol Allergy Clin North Am,2016,36:367-377.
[7] TOMAZIC P V,BIRNER-GRUENBERGER R,LEITNER A,et al.Nasal mucus proteomic changes reflect altered immune responses and epithelial permeability in patients with allergic rhinitis[J].J Allergy Clin Immunol,2014,133:741-750.
[8] TOMAZIC P V,BIRNER-GRUENBERGER R,LEITNER A,et al.Seasonal proteome changes of nasal mucus reflect perennial inflammatory response and reduced defence mechanisms and plasticity in allergic rhinitis[J].J Proteomics,2016,133:153-160.
[9] LEE H J,KIM B,IM N R,et al.Decreased expression of E-cadherin and ZO-1in the nasal mucosa of patients with allergic rhinitis:altered regulation of Ecadherin by IL-4,IL-5,and TNF-alpha[J].Am J Rhinol Allergy,2016,30:173-178.
[10]SONG J,ZHAO H,DONG H,et al.Mechanism of E-cadherin redistribution in bronchial airway epithelial cells in a TDI-induced asthma model[J].Toxicol Lett,2013,220:8-14.
[11]孟楠楠,侯赟,桂岩,等.甲基丁香酚对变应性鼻炎大鼠鼻黏膜组织中黏蛋白5AC的影响[J].浙江大学学报(医学版),2016,45(5):476-484.
[12]SHAH S A,ISHINAGA H,HOU B,et al.Effects of interleukin-31on MUC5AC gene expression in nasal allergic inflammation[J].Pharmacology,2013,91:158-164.
[13] WANG Y,LV L,ZANG H,et al.Regulation of Trek1expression in nasal mucosa with allergic rhinitis by specific immunotherapy[J].Cell Biochem Funct,2015,33:23-28.
[14]RENKONEN J, TOPPILA-SALMIS, JOENVAARA S,et al.Expression of Toll-like receptors in nasal epithelium in allergic rhinitis[J].Apmis,2015,123:716-725.
[15]MOREIRA A P,CAVASSANI K A,ISMAILOGLU U B,et al.The protective role of TLR6in a mouse model of asthma is mediated by IL-23and IL-17A[J].J Clin Invest,2011,121:4420-4432.
[16]CUI X Y,CHEN X,YU C J,et al.Increased expression of toll-like receptors 2and 4and related cytokines in persistent allergic rhinitis[J].Otolaryngol Head Neck Surg,2015,152:233-238.
[17]FRANSSON M,ADNER M,ERJEFALT J,et al.Up-regulation of Toll-like receptors 2,3and 4in allergic rhinitis[J].Respir Res,2005,6:100-104.
[18]VANHINSBERGH L J,POWE D G,JONES N S.Reduction of TLR2gene expression in allergic and nonallergic rhinitis[J].Ann Allergy Asthma Immunol,2007,99:509-516.
[19] LAURIELLO M, MICERA A, MUZI P,et al.TLR4and TLR9Expression in different phenotypes of rhinitis[J].Int J Otolaryngol,2012,2012:925-926.
[20]RYU J H,YOO J Y,KIM M J,et al.Distinct TLRmediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways[J].J Allergy Clin Immunol,2013,131:549-561.
[21]SAKAMOTO M,ASAHINA R,KAMISHINA H,et al.Transcription of thymic stromal lymphopoietin via Toll-like receptor 2in canine keratinocytes:apossible association of Staphylococcus spp.in the deterioration of allergic inflammation in canine atopic dermatitis[J].Vet Dermatol,2016,27:e46.
[22]LI M,WANG Z N,YANG L F,et al.TLR4antagonist suppresses airway remodeling in asthma by inhibiting the T-helper 2response[J].Exp Ther Med,2017,14:2911-2916.
[23]TYURIN Y A,LISSOVSKAYA S A,FASSAHOV R S,et al.Cytokine profile of patients with allergic rhinitis caused by pollen,mite,and microbial allergen sensitization[J].J Immunol Res,2017,2017:305-317.
[24]KITAJIMA M,LEE H C,NAKAYAMA T,et al.TSLP enhances the function of helper type 2cells[J].Eur J Immunol,2011,4:1862-1871.
[25]FROIDURE A,SHEN C,PILETTE C.Dendritic cells revisited in human allergic rhinitis and asthma[J].Allergy,2016,71:137-148.
[26]SOUMELIS V,RECHE P A,KANZLER H,et al.Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP[J].Nat Immunol,2002,3:673-680.
[27]HAN N R,OH H A,NAM S Y,et al.TSLP induces mast cell development and aggravates allergic reactions through the activation of MDM2and STAT6[J].J Invest Dermatol,2014,134:2521-2530.
[28]AKASAKI S,MATSUSHITA K,KATO Y,et al.Murine allergic rhinitis and nasal Th2activation are mediated via TSLP-and IL-33-signaling pathways[J].Int Immunol,2016,28:65-76.
[29]PILETTE C,JACOBSON M R,RATAJCZAK C,et al.Aberrant dendritic cell function conditions Th2-cell polarization in allergic rhinitis[J].Allergy,2013,68:312-321.
[30]ELDER M J,WEBSTER S J,WILLIAMS D L,et al.TSLP production by dendritic cells is modulated by IL-1beta and components of the endoplasmic reticulum stress response[J].Eur J Immunol,2016,46:455-463.
[31]MELUM G R,FARKAS L,SCHEEL C,et al.A thymic stromal lymphopoietin-responsive dendritic cell subset mediates allergic responses in the upper airway mucosa[J].J Allergy Clin Immunol,2014,134:613-621.
[32]ALDINUCCI A,BONECHI E,MANUELLI C,et al.Histamine regulates actin cytoskeleton in human toll-like receptor 4-activated monocyte-derived dendritic cells tuning CD4+T lymphocyte response[J].J Biol Chem,2016,291:14803-14814.
[33]DOHERTY T A,BROIDE D H.Group 2innate lymphoid cells:new players in human allergic diseases[J].J Investig Allergol Clin Immunol,2015,25:1-11.
[34] MAGGI L,MONTAINI G,MAZZONI A,et al.Human circulating group 2innate lymphoid cells can express CD154and promote IgE production[J].J Allergy Clin Immunol,2017,139:964-976.
[35]FAN D,WANG X,WANG M,et al.Allergen-dependent differences in ILC2sfrequencies in patients with allergic rhinitis[J].Allergy Asthma Immunol Res,2016,8:216-222.
[36]DHARIWAL J,CAMERON A,TRUJILLO-TORRALBO M B,et al.Mucosal Type 2Innate lymphoid cells are a key component of the allergic response to aeroallergen[J].Am J Respir Crit Care Med,2017,195:1586-1596.
[37]SALIMI M,BARLOW J L,SAUNDERS S P,et al.A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis[J].J Exp Med,2013,210:2939-2950.
[38]LOZANO N A,SARANZ R J,LOZANO A,et al.Analysis of nasal cytology in children and adolescents with rhinitis[J].Rev Fac Cien Med Univ Nac Cordoba,2017,74:126-133.
[39]JIAO D,WONG C K,QIU H N,et al.NOD2and TLR2ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation[J].Cell Mol Immunol,2016,13:535-550.
[40]LONG H,LIAO W,WANG L,et al.A player and coordinator:the versatile roles of eosinophils in the immune system[J].Transfus Med Hemother,2016,43:96-108.
[41]SALTER B M A,SMITH S G,MUKHERJEE M,et al.Human bronchial epithelial cell-derived factors from severe asthmatic subjects stimulate eosinophil differentiation[J].Am J Respir Cell Mol Biol,2018,58:99-106.
[42]SCHNEIDER E,THIEBLEMONT N,DE MORAES M L,et al.Basophils:new players in the cytokine network[J].Eur Cytokine Netw,2010,21:142-153.
[43]STEINER M,HAWRANEK T,SCHNEIDER M,et al.Elevated Toll-Like receptor-induced cxcl8secretion in human blood basophils from allergic donors is independent of toll-like receptor expression levels[J].PLoS One,2016,11:e0149275.
[44]SUURMOND J,STOOP J N,RIVELLESE F,et al.Activation of human basophils by combined toll-like receptor-and FcepsilonRI-triggering can promote Th2skewing of naive T helper cells[J].Eur J Immunol,2014,44:386-396.
[45]SHIRAISHI Y,JIA Y,DOMENICO J,et al.Sequential engagement of fcepsilonri on mast cells and basophil histamine H(4)Receptor and fcepsilonri in allergic rhinitis[J].J Immunol,2013,190:539-548.
[46]彭海森,朱新华.肥大细胞在变应性鼻炎发病机制中的应用研究[J].临床耳鼻咽喉头颈外科杂志,2018,32(2):157-160.
[47]TONIATO E,FRYDAS I,ROBUFFO I,et al.Activation and inhibition of adaptive immune response mediated by mast cells[J].J Biol Regul Homeost Agents,2017,31:543-548.
[48]CHO M,LEE J E,LIM H,et al.Fibrinogen cleavage products and Toll-like receptor 4promote the generation of programmed cell death 1ligand 2-positive dendritic cells in allergic asthma[J].J Allergy Clin Immunol,2018,142:530-541.
[49] NAHID M A,BENSO L M,SHIN J D,et al.TLR4,TLR7/8agonist-induced miR-146apromotes macrophage tolerance to MyD88-dependent TLR agonists[J].J Leukoc Biol,2016,100:339-349.
[50]TATANO Y,SHIMIZU T,TOMIOKA H.Unique macrophages different from M1/M2 macrophages inhibit T cell mitogenesis while upregulating Th17polarization[J].Sci Rep,2014,4:41-46.
[51]尹雪,任秀敏,刘春苗,等.变应性鼻炎患者IL-35对于Treg/Th17细胞平衡的调控作用[J].临床耳鼻咽喉头颈外科杂志,2016,30(3):213-216.
[52]SUN R,TANG X Y,YANG Y.Immune imbalance of regulatory T/type 2helper cells in the pathogenesis of allergic rhinitis in children[J].J Laryngol Otol,2016,130:89-94.
[53]朱鲁平,程雷.辅助性T细胞与变态反应性疾病的关系[J].中华临床免疫和变态反应杂志,2009,3(4):285-289.
[54]TANG J,XIAO P,LUO X,et al.Increased IL-22level in allergic rhinitis significantly correlates with clinical severity[J].Am J Rhinol Allergy,2014,28:197-201.
[55]GU Z W,WANG Y X,CAO Z W.Neutralization of interleukin-9ameliorates symptoms of allergic rhinitis by reducing Th2,Th9,and Th17responses and increasing the Treg response in a murine model[J].Oncotarget,2017,8:14314-14324.
[56]WANG X Q,HU G H,KANG H Y,et al.High frequency of T helper type 9cells in Chinese patients with allergic rhinitis[J].Asian Pac J Allergy Immunol,2015,33:301-307.
[57]CHENG S,WANG H,ZHOU H.The role of TLR4on B cell activation and anti-beta2GPI antibody production in the antiphospholipid syndrome[J].J Immunol Res,2016,2016:1719-1720.
[58] KOMAI-KOMA M,JONES L,OGG G S,et al.TLR2is expressed on activated T cells as a costimulatory receptor[J].Proc Natl Acad Sci U S A,2004,101:3029-3034.
[59]WU X Z,ZHOU Q,LIN H,et al.Immune regulation of toll-like receptor 2 Engagement on CD4+T cells in murine models of malignant pleural effusion[J].Am J Respir Cell Mol Biol,2017,56:342-352.
[60]REYNOLDS J M,DONG C.Toll-like receptor regulation of effector T lymphocyte function[J].Trends Immunol,2013,34:511-519.
[61]REYNOLDS J M,PAPPU B P,PENG J,et al.Tolllike receptor 2signaling in CD4+T lymphocytes promotes T helper 17responses and regulates the pathogenesis of autoimmune disease[J].Immunity,2010,32:692-702.
[62]WANG X,FAN X,BI S,et al.Toll-like receptors 2and 4-mediated reciprocal Th17and antibody responses to group a streptococcus infection[J].J Infect Dis,2017,215:644-652.
[63]HOSOKI K,BOLDOGH I,SUR S.Innate responses to pollen allergens[J].Curr Opin Allergy Clin Immunol,2015,15:79-88.
[64]祁雪萍,索利敏,赵长青,等.T细胞免疫球蛋白黏蛋白分子4参与变应性鼻炎发病机制的实验研究[J].中华耳鼻咽喉头颈外科杂志,2014,49(4):283-287.
[65]黄雪琨,杨钦泰,陈玉莲,等.γσT细胞、调节性T细胞、白细胞介素17及转化生长因子β1在变应性鼻炎患者外周血中的表达[J].中华耳鼻咽喉头颈外科杂志,2013,48(7):544-548.
[66]SOGUT A,YILMAZ O,KIRMAZ C,et al.Regulatory-T,T-helper 1,and T-helper 2cell differentiation in nasal mucosa of allergic rhinitis with olive pollen sensitivity[J].Int Arch Allergy Immunol,2012,157:349-353.
[67]SAAD K,ZAHRAN A M,ELSAYH K I,et al.Variation of Regulatory T lymphocytes in the peripheral blood of children with allergic rhinitis[J].Arch Immunol Ther Exp(Warsz),2017,66:307-313.
[68]蔡克敏,李华斌,程雷.Foxp3+调节性T细胞及其与鼻部炎性疾病的关系[J].中华临床免疫和变态反应杂志,2010,4(1):61-69.
[69]COOMES S M,KANNAN Y,PELLY V S,et al.CD4+Th2cells are directly regulated by IL-10during allergic airway inflammation[J].Mucosal Immunol,2016,10:150-161.
[70]PALOMARESO, MARTIN-FONTECHAM,LAUENER R,et al.Regulatory T cells and immune regulation of allergic diseases:roles of IL-10 and TGF-beta[J].Genes Immun,2014,15:511-520.
[71]YOKOTA M,SUZUKI M,NAKAMURA Y,et al.Cytokine modulation by IL-35in mice with allergic rhinitis[J].Am J Rhinol Allergy,2015,29:251-256.
[72]WHITEHEAD G S,WILSON R H,NAKANO K,et al.IL-35 production by inducible costimulator(ICOS)-positive regulatory T cells reverses established IL-17-dependent allergic airways disease[J].J Allergy Clin Immunol,2012,129:207-215.
[73]杨光,郑国玺,张璐瑶,等.IL-17及IL-23在变应性鼻炎及非变应性鼻炎患者血清及鼻腔分泌物中的相关表达及意义[J].临床耳鼻咽喉头颈外科杂志,2015,29(12):1086-1090.
[74]GU Z W,WANG Y X,CAO Z W.Neutralization of interleukin-17suppresses allergic rhinitis symptoms by downregulating Th2and Th17responses and upregulating the Treg response[J].Oncotarget,2017,8:22361-22369.
[75]MAKIHARA S,OKANO M,FUJIWARA T,et al.Local expression of interleukin-17ais correlated with nasal eosinophilia and clinical severity in allergic rhinitis[J].Allergy Rhinol(Providence),2014,5:22-27.
[76]QUAN S H,ZHANG Y L,HAN D H,et al.Contribution of interleukin 17Ato the development and regulation of allergic inflammation in a murine allergic rhinitis model[J].Ann Allergy Asthma Immunol,2012,108:342-350.
[77]丁莲富,陈强,李岚,等.舌下特异性免疫治疗过敏性鼻炎/过敏性哮喘患儿IL-17和IL-35水平的变化及临床疗效[J].中国当代儿科杂志,2014,16(12):1206-1210.
[78]DARDALHON V,AWASTHI A,KWON H,et al.IL-4inhibits TGF-beta-induced Foxp3+T cells and,together with TGF-beta,generates IL-9+IL-10+Foxp3(-)effector T cells[J].Nat Immunol,2008,9:1347-1355.
[79]FROIDURE A,SHEN C,GRAS D,et al.Myeloid dendritic cells are primed in allergic asthma for thymic stromal lymphopoietin-mediated induction of Th2and Th9responses[J].Allergy,2014,69:1068-1076.
[80]PALAGA T.Driving forces of inflammatory diseases:Th9in allergic rhinitis and estrogen in SLE[J].Asian Pac J Allergy Immunol,2015,33:265-266.
[81]WANG X Q,KE X,SHEN Y,et al.Changes in circulating follicular helper T-cells in Chinese patients with allergic rhinitis[J].Acta Otolaryngol,2016,136:199-204.
[82]BALLESTEROS-TATO A,RANDALL T D.Priming of T follicular helper cells by dendritic cells[J].Immunol Cell Biol,2014,92:22-27.
[83]KAMEKURA R,SHIGEHARA K,MIYAJIMA S,et al.Alteration of circulating type 2follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma[J].Clin Immunol,2015,158:204-211.
[84]KIM A S,DOHERTY T A,KARTA M R,et al.Regulatory B cells and T follicular helper cells are reduced in allergic rhinitis[J].J Allergy Clin Immunol,2016,138:1192-1195.
[85]HE J S,NARAYANAN S,SUBRAMANIAM S,et al.Biology of IgE production:IgE cell differentiation and the memory of IgE responses[J].Curr Top Microbiol Immunol,2015,388:1-19.
[86]MATSUSHITA K,YOSHIMOTO T.B cell-intrinsic MyD88signaling is essential for IgE responses in lungs exposed to pollen allergens[J].J Immunol,2014,193:5791-5800.