Increased expression of type 2 innate lymphoid cells in pediatric patients with allergic rhinitis

Sun,Rong; Yang,Yang; Huo,Qianzhu; Gu,Zheng; Wei,Ping; Tang,Xinye

doi:10.3892/etm.2019.8235

Increased expression of type 2 innate lymphoid cells in pediatric patients with allergic rhinitis

Authors:
- Rong Sun
- Yang Yang
- Qianzhu Huo
- Zheng Gu
- Ping Wei
- Xinye Tang
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Affiliations: Department of Physical Examination, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Otolaryngology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China
Published online on: November 22, 2019 https://doi.org/10.3892/etm.2019.8235
Pages: 735-740

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Abstract

Type 2 innate lymphoid cells (ILC2s) are a newly identified group of innate immune cells. ILC2s promote features of allergic airway diseases through the secretion of Th2 type cytokines, including interleukin (IL)‑4, IL‑5 and IL‑13. It remains unknown whether ILC2s aggregate in the peripheral blood. The present study examined the ILC2 levels in pediatric patients with allergic rhinitis (AR), and the correlation with the severity of clinical symptoms. Flow cytometry detected the ILC2s frequency in the peripheral blood of 12 healthy controls (HCs), 12 patients with AR sensitized only to house dust mites (HDM‑AR), and 18 AR patients monosensitized to other antigens including weeds, animal danders and Blattella germanica, but not including HDM (non‑HDM‑AR). Clinical symptoms of AR were expressed according to the Total 5 Symptom Score (T5SS). The percentages of ILC2s in the peripheral blood were increased significantly in patients with HDM‑AR and non‑HDM‑AR, compared with that in the HCs. A subgroup analysis of patients with AR indicated that the proportion of ILC2s was significantly increased in HDM‑AR in comparison with that in non‑HDM AR. Furthermore, there was a notable correlation between ILC2 levels and T5SS scores. ILC2s frequencies in PBMC were increased significantly in pediatric patients with AR, irrespective of the type of allergen. HDM may trigger more severe allergic reactions and an increase in the number of ILC2s. These discoveries indicate the unique function of ILC2 in AR and provide a potential therapeutic target.

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1	Seidman MD, Gurgel RK, Lin SY, Schwartz SR, Baroody FM, Bonner JR, Dawson DE, Dykewicz MS, Hackell JM, Han JK, et al: Guideline otolaryngology development group. AAO-HNSF. Clinical practice guideline: Allergic rhinitis. Otolaryngol Head Neck Surg. 152 (Suppl 1):S1–S43. 2015. View Article : Google Scholar : PubMed/NCBI
2	Bachert C, Wagenmann M and Holtappels G: Cytokines and adhesion molecules in allergic rhinitis. Am J Rhinol. 12:3–8. 1998. View Article : Google Scholar : PubMed/NCBI
3	Wang DY and Clement P: Pathogenic mechanisms underlying the clinical symptoms of allergic rhinitis. Am J Rhinol. 14:325–333. 2000. View Article : Google Scholar : PubMed/NCBI
4	Pawankar R, Mori S, Ozu C and Kimura S: Overview on the pathomechanisms of allergic rhinitis. Asia Pac Allergy. 1:157–167. 2011. View Article : Google Scholar : PubMed/NCBI
5	Cavagnero K and Doherty TA: Cytokine and lipid mediator regulation of group 2 innate lymphoid cells (ILC2s) in human allergic airway disease. J Cytokine Biol. 2(pii): 1162017.PubMed/NCBI
6	Björkström NK, Kekäläinen E and Mjösberg J: Tissue-specific effector functions of innate lymphoid cells. Immunology. 139:416–427. 2013. View Article : Google Scholar : PubMed/NCBI
7	Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie AN, Mebius RE, et al: Innate lymphoid cells-a proposal for uniform nomenclature. Nat Rev Immunol. 13:145–149. 2013. View Article : Google Scholar : PubMed/NCBI
8	Bartemes KR, Kephart GM, Fox SJ and Kita H: Enhanced innate type 2 immune response in peripheral blood from patients with asthma. J Allergy Clin Immunol. 134:671–678.e4. 2014. View Article : Google Scholar : PubMed/NCBI
9	Doherty TA, Scott D, Walford HH, Khorram N, Lund S, Baum R, Chang J, Rosenthal P, Beppu A, Miller M and Broide DH: Allergen challenge in allergic rhinitis rapidly induces increased peripheral blood type 2 innate lymphoid cells that express CD84. J Allergy Clin Immunol. 133:1203–1205. 2014. View Article : Google Scholar : PubMed/NCBI
10	Fan D, Wang X, Wang M, Wang Y, Zhang L, Li Y, Fan E, Cao F, Van Crombruggen K, Zhang L, et al: Allergen-dependent differences in ILC2s frequencies in patients with allergic rhinitis. Allergy Asthma Immunol Res. 8:216–222. 2016. View Article : Google Scholar : PubMed/NCBI
11	Bousquet J, Schünemann HJ, Samolinski B, Demoly P, Baena-Cagnani CE, Bachert C, Bonini S, Boulet LP, Bousquet PJ, Brozek JL, et al: Allergic rhinitis and its impact on asthma (ARIA): Achievements in 10 years and future needs. J Allergy Clin Immunol. 130:1049–1062. 2012. View Article : Google Scholar : PubMed/NCBI
12	Bousquet J, Bachert C, Canonica GW, Mullol J, Van Cauwenberge P, Bindslev Jensen C, Fokkens WJ, Ring J, Keith P, Lorber R, et al: Efficacy of desloratadine in intermittent allergic rhinitis: A GA (2)LEN study. Allergy. 64:1516–1523. 2009. View Article : Google Scholar : PubMed/NCBI
13	Pilette C, Jacobson MR, Ratajczak C, Detry B, Banfield G, VanSnick J, Durham SR and Nouri-Aria KT: Aberrant dendritic cell function conditions Th2-cell polarization in allergic rhinitis. Allergy. 68:312–321. 2013. View Article : Google Scholar : PubMed/NCBI
14	Skrindo I, Ballke C, Gran E, Johansen FE, Baekkevold ES and Jahnsen FL: IL-5 production by resident mucosal allergen-specific T cells in an explant model of allergic rhinitis. Clin Exp Allergy. 45:1296–1304. 2015. View Article : Google Scholar : PubMed/NCBI
15	Lao-Araya M, Steveling E, Scadding GW, Durham SR and Shamji MH: Seasonal increases in peripheral innate lymphoid type 2 cells are inhibited by subcutaneous grass pollen immunotherapy. J Allergy Clin Immunol. 134:1193–1195.e4. 2014. View Article : Google Scholar : PubMed/NCBI
16	Zhong H, Fan XL, Yu QN, Qin ZL, Chen D, Xu R, Chen DH, Lin ZB, Wen W and Fu QL: Increased innate type 2 immune response in house dust mite-allergic patients with allergic rhinitis. Clin Immunol. 183:293–299. 2017. View Article : Google Scholar : PubMed/NCBI
17	Christianson CA, Goplen NP, Zafar I, Irvin C, Good JT Jr, Rollins DR, Gorentla B, Liu W, Gorska MM, Chu H, et al: Persistence of asthma requires multiple feedback circuits involving type 2 innate lymphoid cells and IL-33. J Allergy Clin Immunol. 136:59–68.e14. 2015. View Article : Google Scholar : PubMed/NCBI
18	Nagakumar P, Denney L, Fleming L, Bush A, Lloyd CM and Saglani S: type 2 innate lymphoid cells in induced sputum from children with severe asthma. J Allergy Clin Immunol. 137:624–626.e6. 2016. View Article : Google Scholar : PubMed/NCBI
19	Mjösberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B, Fokkens WJ, Cupedo T and Spits H: Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat Immunol. 12:1055–1062. 2011. View Article : Google Scholar : PubMed/NCBI
20	Walford HH, Lund SJ, Baum RE, White AA, Bergeron CM, Husseman J, Bethel KJ, Scott DR, Khorram N, Miller M, et al: Increased ILC2s in the eosinophilic nasal polyp endotype are associated with corticosteroid responsiveness. Clin Immunol. 155:126–135. 2014. View Article : Google Scholar : PubMed/NCBI
21	Miljkovic D, Bassiouni A, Cooksley C, Ou J, Hauben E, Wormald PJ and Vreugde S: Association between group 2 innate lymphoid cells enrichment, nasal polyps and allergy in chronic rhinosinusitis. Allergy. 69:1154–1161. 2014. View Article : Google Scholar : PubMed/NCBI
22	Ho J, Bailey M, Zaunders J, Mrad N, Sacks R, Sewell W and Harvey RJ: Group 2 innate lymphoid cells (ILC2s) are increased in chronic rhinosinusitis with nasal polyps or eosinophilia. Clin Exp Allergy. 45:394–403. 2015. View Article : Google Scholar : PubMed/NCBI
23	Eastman JJ, Cavagnero KJ, Deconde AS, Kim AS, Karta MR, Broide DH, Zuraw BL, White AA, Christiansen SC, Doherty TA, et al: Group 2 innate lymphoid cells are recruited to the nasal mucosa in patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 140:101–108.e3. 2017. View Article : Google Scholar : PubMed/NCBI
24	Doherty TA: At the bench: Understanding group 2 innate lymphoid cells in disease. J Leukoc Biol. 97:455–467. 2015. View Article : Google Scholar : PubMed/NCBI
25	Johansson K, Malmhäll C, Ramos-Ramírez P and Rådinger M: Bone marrow type 2 innate lymphoid cells: A local source of interleukin-5 in interleukin-33-driven eosinophilia. Immunology. 153:268–278. 2018. View Article : Google Scholar : PubMed/NCBI
26	Xue L, Salimi M, Panse I, Mjösberg JM, McKenzie AN, Spits H, Klenerman P and Ogg G: Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells. J Allergy Clin Immunol. 133:1184–1194. 2014. View Article : Google Scholar : PubMed/NCBI
27	Salimi M, Stöger L, Liu W, Go S, Pavord I, Klenerman P, Ogg G and Xue L: Cysteinyl leukotriene E₄ activates human group 2 innate lymphoid cells and enhances the effect of prostaglandin D₂ and epithelial cytokines. J Allergy Clin Immunol. 140:1090–1100.e11. 2017. View Article : Google Scholar : PubMed/NCBI
28	Doherty TA, Khorram N, Lund S, Mehta AK, Croft M and Broide DH: Lung type 2 innate lymphoid cells express cysteinyl leukotriene receptor 1, which regulates TH2 cytokine production. J Allergy Clin Immunol. 132:205–213. 2013. View Article : Google Scholar : PubMed/NCBI
29	Miao Q, Wang Y, Liu YG, Ren YX, Guan H, Li Z, Xu W and Xiang L: Seasonal variation in circulating group 2 innate lymphoid cells in mugwort-allergic asthmatics during and outside pollen season. Allergy Asthma Clin Immunol. 14:62018. View Article : Google Scholar : PubMed/NCBI
30	Wang XY, Ma TT, Wang XY, Zhuang Y, Wang XD, Ning HY, Shi HY, Yu RL, Yan D, Huang HD, et al: Prevalence of pollen-induced allergic rhinitis with high pollen exposure in grasslands of northern China. Allergy. 73:1232–1243. 2018. View Article : Google Scholar : PubMed/NCBI
31	Chen K, Liao YF and Zhang JT: The major aeroallergens in Guangxi, China. Clin Allergy. 18:589–596. 1988. View Article : Google Scholar : PubMed/NCBI
32	Jahn-Schmid B, Kelemen P, Himly M, Bohle B, Fischer G, Ferreira F and Ebner C: The T cell response to Art v 1, the major mugwort pollen allergen, is dominated by one epitope. J Immunol. 169:6005–6011. 2002. View Article : Google Scholar : PubMed/NCBI
33	Fu W, Gao Z, Gao L, Jin J, Liu M, Sun Y, Wu S, Wu L, Ma H, Dong Y, et al: Identification of a 62-kDa major allergen from Artemisia pollen as a putative galactose oxidase. Allergy. 73:1041–1052. 2017. View Article : Google Scholar
34	Wopfner N, Gadermaier G, Egger M, Asero R, Ebner C, Jahn-Schmid B and Ferreira F: The spectrum of allergens in ragweed and mugwort pollen. Int Arch Allergy Immunol. 138:337–346. 2005. View Article : Google Scholar : PubMed/NCBI
35	Yu CK and Chen CL: Activation of mast cells is essential for development of house dust mite Dermatophagoides farinae-induced allergic airway inflammation in mice. J Immunol. 171:3808–3815. 2003. View Article : Google Scholar : PubMed/NCBI
36	Chu DK, Llop-Guevara A, Walker TD, Flader K, Goncharova S, Boudreau JE, Moore CL, Seunghyun In T, Waserman S, Coyle AJ, et al: IL-33, but not thymic stromal lymphopoietin or IL-25, is central to mite and peanut allergic sensitization. J Allega Clin Immunol. 131:187–200.e1-8. 2013. View Article : Google Scholar
37	Jia Y, Fang X, Zhu X, Bai C, Zhu L, Jin M, Wang X, Hu M, Tang R and Chen Z: IL-13+ type 2 innate lymphoid cells correlate with asthma control status and treatment response. Am J Respir Cell Mol Biol. 55:675–683. 2016. View Article : Google Scholar : PubMed/NCBI
38	Wang H, Lin J, Zeng L, Ouyang C, Ran P, Yang P and Liu Z: Der f 31, a novel allergen from Dermatophagoides farinae, activates epithelial cells and enhances lung-resident group 2 innate lymphoid cells. Sci Rep. 7:85192017. View Article : Google Scholar : PubMed/NCBI
39	Smith SG, Chen R, Kjarsgaard M, Huang C, Oliveria JP, O'Byrne PM, Gauvreau GM, Boulet LP, Lemiere C, Martin J, et al: Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia. J Allergy Clin Immunol. 137:75–86.e8. 2016. View Article : Google Scholar : PubMed/NCBI