TO IDENTIFY THE EXPRESSION OF INTRACELLULAR TOLL-LIKE RECEPTORS (TLRS) IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF ALOPECIA AREATA
Main Article Content
Keywords
Alopecia areata, autoimmune, gene expression, hair follicles, RT-qPCR, toll like receptors, SALT-score
Abstract
Background Alopecia areata (AA) is a hair loss of scalp with out scarring and other hair bearing area. In AA immune system invade hair follicles The innate immunity and Toll-like receptors (TLRs) can express significant role in this autoimmune disorder. According to available data the role of expression of TLRs studied in multiple cutaneous disorders; however, some were investigated in relation to pathogenesis of AA
Methodology This retrospective cross-sectional study is to investigate the role of TLR-3, TLR-7, TLR-8, and TLR-9 in the AA patients. 40 (AA) patients were recruited from the Institute of Skin Disease Sindh and 10 healthy controls after getting an informed consent. Venous whole blood was used to extract the total RNA, and by using a real time quantitative PCR (RT-qPCR) expression of four TLRs with GAPDH (a house-keeping gene) was determined. The ANOVA statistical test was applied to analyze the expression values.
Results The expressions of all the four TLRs in AA were considerably significant than in the controls. The average relative expression of TLR-3, TLR-7, TLR-8, and TLR-9 was 54.40, 111.69, 34.45, and 112.51 respectively in all the AA patients. By comparing between male and female AA patients, the expression of all the four TLRs was non-significantly higher in male AA patients (p<0.5). TLRs expression was observed highest in the age group 21-30 yrs.
Conclusion This study identifies the significance of TLRs expression in AA patients indicating the fundamental role in autoimmunity, which will further provide a new insight in the therapeutic strategies of AA and other linked cutaneous diseases. Furthermore, studies are required to understand the targeted TLRs expression in introducing new modulated therapies for management of AA patients.
References
1. Brzezińska-Wcisło L, Bergler-Czop B, Wcisło-Dziadecka D, Lis-Święty A. New aspects of the treatment of alopecia areata. Advances in Dermatology and Allergology. 2014;31(4):262-5.
2. Pratt CH, King LE, Messenger AG, Christiano AM, Sundberg JP. Alopecia areata. Nature Reviews Disease Primers. 2017;3(1):17011.
3. Toussi A, Barton VR, Le ST, Agbai ON, Kiuru M. Psychosocial and psychiatric comorbidities and health-related quality of life in alopecia areata: a systematic review. Journal of the American Academy of Dermatology. 2021;85(1):162-75.
4. Jabbari A, Cerise JE, Chen JC, Mackay-Wiggan J, Duvic M, Price V, et al. Molecular signatures define alopecia areata subtypes and transcriptional biomarkers. EBioMedicine. 2016;7:240-7.
5. Islam N, Leung PS, Huntley AC, Gershwin ME. The autoimmune basis of alopecia areata: a comprehensive review. Autoimmunity Reviews. 2015;14(2):81-9.
6. Rajabi F, Drake L, Senna M, Rezaei N. Alopecia areata: a review of disease pathogenesis. British Journal of Dermatology. 2018;179(5):1033-48.
7. Bertolini M, McElwee K, Gilhar A, Bulfone‐Paus S, Paus R. Hair follicle immune privilege and its collapse in alopecia areata. Experimental Dermatology. 2020;29(8):703-25.
8. Simakou T, Butcher JP, Reid S, Henriquez FL. Alopecia areata: A multifactorial autoimmune condition. Journal of Autoimmunity. 2019;98:74-85.
9. Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, et al. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nature Medicine. 2014;20(9):1043-9.
10. Koenderman L, Buurman W, Daha MR. The innate immune response. Immunology letters. 2014;162(2):95-102.
11. Botos I, Segal DM, Davies DR. The structural biology of Toll-like receptors. Structure. 2011;19(4):447-59.
12. Asami J, Shimizu T. Structural and functional understanding of the toll‐like receptors. Protein Science. 2021;30(4):761-72.
13. Behzadi P, García-Perdomo HA, Karpiński TM. Toll-like receptors: general molecular and structural biology. Journal of Immunology Research. 2021;2021:1-21.
14. Li D, Wu M. Pattern recognition receptors in health and diseases. Signal Transduction and Targeted Therapy. 2021;6(1):291.
15. Kaisho T, Akira S. Toll-like receptor function and signaling. The Journal of allergy and clinical immunology. 2006;117(5):979-87; quiz 88.
16. Akira S, Hemmi H. Recognition of pathogen-associated molecular patterns by TLR family. Immunology letters. 2003;85(2):85-95.
17. Gohar A, Shakeel M, Atkinson RL, Haleem DJ. Potential mechanisms of improvement in body weight, metabolic profile, and liver metabolism by honey in rats on a high fat diet. PharmaNutrition. 2020;14:100227.
18. Toubi E, Vadasz Z. Innate immune-responses and their role in driving autoimmunity. Autoimmun Rev. 2019;18(3):306-11.
19. Alzolibani AA, Rasheed Z, Bin Saif G, Al-Dhubaibi MS, Al Robaee AA. Altered expression of intracellular Toll-like receptors in peripheral blood mononuclear cells from patients with alopecia areata. BBA clinical. 2016;5:134-42.
20. Krieg AM, Vollmer J. Toll-like receptors 7, 8, and 9: linking innate immunity to autoimmunity. Immunological reviews. 2007;220:251-69.
21. Zainol MIB, Kawasaki T, Monwan W, Murase M, Sueyoshi T, Kawai T. Innate immune responses through Toll-like receptor 3 require human-antigen-R-mediated Atp6v0d2 mRNA stabilization. Scientific Reports. 2019;9(1):20406.
22. Wagner H. Interactions between bacterial CpG-DNA and TLR9 bridge innate and adaptive immunity. Current opinion in microbiology. 2002;5(1):62-9.
23. Sun Y, Reddy P. CH 18 - Intracellular sensors of immunity and allogeneic hematopoietic stem cell transplantation. In: Socié G, Blazar BR, editors. Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation. San Diego: Academic Press; 2013. p. 425-47.
24. Alexoudi I, Kapsimali V, Vaiopoulos A, Kanakis M, Vaiopoulos G. Toll-like receptors pathways implication in common autoimmune diseases and therapeutic perspectives. Giornale italiano di dermatologia e venereologia: organo ufficiale, Societa italiana di dermatologia e sifilografia. 2015;150(2):255-60.
25. Kang H, Wu W-Y, Yu M, Shapiro J, McElwee KJ. Increased expression of TLR7 and TLR9 in alopecia areata. Experimental Dermatology. 2020;29(3):254-8.
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Dr. Muhammad Suleman Pirzado
PhD Assistant Professor. Department of Molecular Biology and Genetics, Liaquat University of Health Sciences, Jamshoro.
Sobia Wali Muhammad
PhD Scholar. MRC Clinical Sciences Liaquat University of Medical & Health Sciences, Jamshoro.