Main Article Content
Asthma is the most frequent noncommunicable disease and one of the leading causes of years lived with disability. Asthma has a severe impact on a patient's life, being able to disturb the activities of both children and adults. The morbidity and mortality of asthma may depend on the severity and progressiveness of the symptoms experienced by the patient. Different and complex pathomechanisms underline the pathology of asthma, in which the regulation of innate and adaptive immune responses plays a role. There is a complex interaction between immune cells including chemokines involved in the pathogenesis of asthma. Immune cell trafficking is orchestrated by a family of small proteins called chemokines. Leukocytes express cell-surface receptors that bind to chemokines and trigger transendothelial migration. This review article outlines the main role of chemokines in inflammatory reactions that occur in allergic asthma, based on the latest literature studies that have been published previously. The allergic reaction in asthma expresses various chemokines and their receptors. Chemokines including eotaxins (CCL11, CCL24, and CCL26), CCL2, CCL5, CCL17, and CCL22 regulate immune cells that under pathological conditions travel to the inflammatory site, mainly in the lung, to protect the body from pathogen invasion. Chemokines are released by a number of immune cells such as monocytes, dendritic cells, mast cells, and epithelial cells in the airway. The biological effects of chemokine production are enhanced by secreted cytokines when an allergic reaction occurs in asthma, such as IL-4, IL-5, and IL-13. Chemokines cause an accumulation of different inflammatory cells at the site of inflammation, which ultimately results in tissue damage to the airway. The inhibition of the reactions evoked by the interaction between chemokines and their receptors is considered a candidate for the development of potent therapeutic drugs for asthma in the future.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The journal allows the authors to hold the copyright without restrictions and allow the authors to retain publishing rights without restrictions.
. Almatroudi A, Mousa AM, Vinnakota D, et al. Prevalence and associated factors of respiratory allergies in the Kingdom of Saudi Arabia: a cross-sectional investigation, September-December 2020. PLoS ONE 2021;16:e0253558. doi.org/10.1371/journal.pone.0253558.
Keshavarz B, Erickson LD, Platts-Mills TAE, Wilson JM. Lessons in innate and allergic immunity from dust mite feces and tick bites. Front Allergy 2021;2:692643. doi: 10.3389/falgy.2021. 692643.
Fuhlbrigge AL. Epidemiology of asthma, COPD, and asthma-COPD overlap. In: Bernstein JA, Boulet L-P, Wechsler ME, editors. Asthma, COPD, and overlap: a case-based overview of similarities and differences. Boca Raton: CRC Press; 2018. p. 13–4.
Global Initiative for Asthma. 2022 GINA report, global strategy for asthma management and prevention. Fontana (WI): Global Initiative for Asthma; c2022.
Khweek AA, Kim E, Joldrichsen MR, Amer AO, Boyaka PN. Insights into mucosal innate immune responses in house dust mite-mediated allergic asthma. Front Immunol 2020;11:534501. doi: 10.3389/fimmu.2020.534501.
Centers for Disease Control and Prevention. Asthma prevalence and health care, resource utilization estimates, United States, 2001-2017. Atlanta (GA): Centers for Disease Control and Prevention; 2021.
Vos T, Lim SS, Abbafati C, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020;396:1204–22. doi: 10.1016/S0140-6736(20)30925-9.
Kementerian Kesehatan Republik Indonesia. Laporan Nasional RISKESDAS 2018. Jakarta: Badan Penelitian dan Pengembangan Kesehatan; 2019.
Global Asthma Network. The Global Asthma Report 2018. New Zealand; 2018.
Mahmoudi M, editor. Allergy and asthma: the basics to best practices. Switzerland: Springer Nature Switzerland AG; 2019.
Castan L, Magnan A, Bouchaud G. Chemokine receptors in allergic diseases. Allergy 2017;72: 682–90. doi: 10.1111/all.13089.
Pavón-Romero GF, Serrano-Pérez NH, García-Sánchez L, Ramírez-Jiménez F, Terán LM. Neuroimmune pathophysiology in asthma. Front Cell Dev Biol 2021;9:663535. doi: 10.3389/fcell. 2021.663535.
Berghi NO, Dumitru M, Vrinceanu D, et al. Relationship between chemokines and T lymphocytes in the context of respiratory allergies. Exp Ther Med 2020;20:2352–60. doi: 10.3892/etm.2020.8961.
Mubarak B, Shakoor H, Masood F. Eosinophilic asthma. In: Pereira C, editor. Asthma -biological evidences IntechOpen; 2019.
Hashmi MF, Tariq M, Cataletto ME. Asthma. Treasure Island (FL): StatPearls Publishing; 2021.
Esteban-Gorgojo I, Antolín-Amérigo D, Domínguez-Ortega J, Quirce S. Non-eosinophilic asthma: current perspectives. J Asthma Allergy 2018;11:267–81. doi: 10.2147/JAA.S153097.
Fildan AP, Rajnoveanu R-M, Cirjaliu R, et al. Biological therapies targeting the type 2 inflammatory pathway in severe asthma. Exp Ther Med 2021;22:1263. doi: 10.3892/etm.2021.10698.
Al-Moamary MS, Alhaider SA, Alangari AA, et al. The Saudi initiative for asthma - 2021 update: guidelines for the diagnosis and management of asthma in adults and children. Ann Thorac Med 2021;16:4–56. doi: 10.4103/atm.ATM_697_20.
Rogliani P, Calzetta L, Matera MG, et al. Severe asthma and biological therapy: when, which, and for whom. Pulm Ther 2020;6:47–66. doi: 10.1007/s41030-019-00109-1.
Sze E, Bhalla A, Nair P. Mechanisms and therapeutic strategies for non-T2 asthma. Allergy 2020;75:311–25. doi: 10.1111/all.13985.
Fergeson JE, Patel SS, Lockey RF. Acute asthma, prognosis, and treatment. J Allergy Clin Immunol 2016;139:438–47. doi: 10.1016/j.jaci.2016.06.054.
Chesnutt AN, Chesnutt MS, Prendergast NT, Prendergast TJ. Pathophysiology of disease: an introduction to clinical medicine. In: Papadakis MA, McPhee SJ, Rabow MW, McQuaid KR, editors. Current Medical Diagnosis & Treatment 2020. 59th ed. New York: McGraw-Hill Education; 2020. p. 625–34.
Pandey R, Parkash V, Kant S, et al. An update on the diagnostic biomarkers for asthma. J Fam Med Prim Care 2021;10:1139–48. doi: 10.4103/jfmpc. jfmpc_2037_20.
Kaur R, Chupp G. Phenotypes and endotypes of adult asthma: moving toward precision medicine. J Allergy Clin Immunol 2019;144:1-12. doi: 10.1016/j.jaci.2019.05.031.
Jaeger K, Bruenle S, Weinert T, et al. Structural basis for allosteric ligand recognition in the human CC chemokine receptor 7. Cell 2019;178: 1222-30.e10. doi: 10.1016/j.cell.2019.07.028.
Stone MJ, Hayward JA, Huang C, Huma ZE, Sanchez J. Mechanisms of regulation of the chemokine-receptor network. Int J Mol Sci 2017; 18:342. doi: 10.3390/ijms18020342.
Bhusal RP, Foster SR, Stone MJ. Structural basis of chemokine and receptor interactions: key regulators of leukocyte recruitment in inflammatory responses. Protein Sci 2020;29:420–32. doi: 10.1002/pro.3744.
Dembic Z. The cytokines of the immune system: the role of cytokines in diseases related to immune response. 1st ed. USA: Elsevier Inc.; 2015.
Murphy PM. Chemokines and chemokine receptors. In: Rich RR, Fleisher TA, Shearer WT, et al., editors. Clinical immunology: principles and practice. 5th ed. China: Elsevier; 2019.p.157–63.
Stone MJ. Regulation of chemokine-receptor interactions and functions. Int J Mol Sci 2017;18: 2415. doi: 10.3390/ijms18112415.
Arimont M, Sun SL, Leurs R, Smit I, de Esch JP, de Graaf C. Structural analysis of chemokine receptor-ligand interactions. J Med Chem 2017;60: 4735–79. doi: 10.1021/acs.jmedchem.6b01309.
Sowa JE, Tokarski K. Cellular, synaptic, and network effects of chemokines in the central nervous system and their implications to behavior. Pharmacol Reports 2021;73:1595–625. doi: 10.1007/s43440-021-00323-2.
Patel J, Channon KM, McNeill E. The downstream regulation of chemokine receptor signalling: implications for atherosclerosis. Mediators Inflamm 2013;2013:459520. doi: 10.1155/2013/459520.
Bissonnette EY, Lauzon-Joset J-F, Debley JS, Ziegler SF. Cross-talk between alveolar macrophages and lung epithelial cells is essential to maintain lung homeostasis. Front Immunol 2020;11:583042. doi: 10.3389/fimmu.2020.583042.
Komlósi ZI, van de Veen W, Kovács N, et al. Cellular and molecular mechanisms of allergic asthma. Mol Aspects Med 2022;85:100995. doi: 10.1016/j.mam.2021.100995.
Zajkowska M, Mroczko B. From allergy to cancer—clinical usefulness of eotaxins. Cancers 2021;13:128. doi: 10.3390/cancers13010128.
Liu C, Zhang X, Xiang Y, et al. Role of epithelial chemokines in the pathogenesis of airway inflammation in asthma. Mol Med Rep 2018;17:6935–41. doi: 10.3892/mmr.2018.8739.
Bakakos A, Loukides S, Bakakos P. Severe eosinophilic asthma. J Clin Med 2019;8:1375. doi: 10.3390/jcm8091375.
Abdelaziz MH, Abdelwahab SF, Wan J, et al. Alternatively activated macrophages; A double-edged sword in allergic asthma. J Transl Med 2020;18:1–12. doi: 10.1186/s12967-020-02251-w.
Catherine J, Roufosse F. What does elevated TARC/CCL17 expression tell us about eosinophilic disorders? Semin Immunopathol 2021;43:439–58. doi: 10.1007/s00281-021-00857-w.
Rapp M, Wintergerst MWM, Kunz WG, et al. CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes. J Exp Med 2019;216:1170–81. doi: 10.1084/jem.20170277.
Velikova T V, Krasimirova E, Lazova SM, et al. MCP-1/CCL2 in a Bulgarian cohort of children with bronchial asthma and cystic fibrosis. Arch Immunol Allergy 2018;1:1–5.
Wang XZ, Zhang HH, Qian YL, Tang LF. Sonic hedgehog (Shh) and CC chemokine ligand 2 signaling pathways in asthma. J Chin Med Assoc 2019;82:343–50. doi: 10.1097/JCMA. 0000000000000094.
Bawazeer MA, Theoharides TC. IL-33 stimulates human mast cell release of CCL5 and CCL2 via MAPK and NF-êB, inhibited by methoxyluteolin. Eur J Pharmacol 2019;865:172760. doi: 10.1016/j.ejphar.2019.172760.
Alturaiki WH. Evaluation of C-C chemokine ligand 5 (CCL5) chemokine, interleukin 5 (IL-5) cytokine, and eosinophil counts as potential biomarkers in Saudi patients with chronic asthma during sandstorms. Cureus 2020;12:e7809. doi: 10.7759/cureus.7809.
Busse WW, Kraft M, Rabe KF, et al. Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation. Eur Respir J 2021;58:2003393. doi: 10.1183/13993003.03393-2020.
Aoki A, Hirahara K, Kiuchi M, Nakayama T. Eosinophils: cells known for over 140 years with broad and new functions. Allergol Int 2021;70:3–8. doi: 10.1016/j.alit.2020.09.002.
Palomino DCT, Marti LC. Chemokines and immunity. Einstein (Sao Paulo) 2015;13:469–73. doi: 10.1590/S1679-45082015RB3438.
Ding Q, Sun S, Zhang Y, et al. Serum IL-8 and VEGFA are two promising diagnostic biomarkers of asthma-COPD overlap syndrome. Int J Chron Obstruct Pulmon Dis 2020;15:357–65. doi: 10.2147/COPD.S233461.
Kyriakopoulos C, Gogali A, Bartziokas K, Kostikas K. Identification and treatment of T2-low asthma in the era of biologics. ERJ Open Res 2021;7:00309–2020. doi: 10.1183/23120541.00309-2020.
Nakagome K, Nagata M. Involvement and possible role of eosinophils in asthma exacerbation. Front Immunol 2018;9:2220. doi: 10.3389/fimmu.2018.02220.
Huoman J, Haider S, Simpson A, et al. Childhood CCL18, CXCL10 and CXCL11 levels differentially relate to and predict allergy development. Pediatr Allergy Immunol 2021;32:1824–32. doi: 10.1111/pai.13574.
Hatami H, Ghaffari N, Ghaffari J, Rafatpanah H. Role of cytokines and chemokines in the outcome of children with severe asthma. J Pediatr Rev 2019; 7:17–28. doi: 10.32598/jpr.7.1.17.