Intracytoplasmic and Plasma Cytokine Levels of Natural Killer Cells in Patients with Asthma

Akdeniz, Nilg�n; �etin, Esin; Erten Yurdag�l, Gaye; Y�lmaz, Vuslat; Gemicioglu, Bilun; Deniz, G�nnur

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Intracytoplasmic and Plasma Cytokine Levels of Natural Killer Cells in Patients with Asthma [Turk J Immunol]

Turk J Immunol. 2021; 9(2): 86-94 | DOI: 10.5222/TJI.2021.42714

Intracytoplasmic and Plasma Cytokine Levels of Natural Killer Cells in Patients with Asthma

Nilg�n Akdeniz¹, Esin �etin¹, Gaye Erten Yurdag�l¹, Vuslat Y�lmaz², Bilun Gemicioglu³, G�nnur Deniz¹
¹Istanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Immunology, Istanbul, Turkey
²Istanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Neuscience, Istanbul, Turkey
³Istanbul University Cerrahpasa, Cerrahpasa Faculty of Medicine, Department of Pulmonary Diseases, Istanbul, Turkey

Objective: Natural killer cells play immunomodulatory role the pathogenesis of chronic inflammatory airway diseases. NK cells may induce allergic airway inflammation by increasing the production of type 2 cytokines.
Materials and Methods: We measured intracytoplasmic cytokine levels of IL-13, IL-4, IFNγ and IL-10 in NK cells and serum levels of IFN-γ, TNF-α, IL-2, IL-8, IL-4, IL-5, IL-6, IL-17, IL12, IL-13, IL-1β and IL-10 in patients with newly diagnosed asthma, asthmatic patients under treatment (UT) and controls by using flow cytometry and ProcartaPlex multiplex immunoassays kit.
Result: IFN-γ+NK1 cells were decreased in both patient groups; comparing both asthmatic groups, IFN-γ+NK1 cells were higher in asthmatics UT. Intracellular IL-4 of NK cells were higher in both patient groups vs. controls. IL-10+NK cells were lower in both patient groups vs. controls. We detected increased numbers of IL-13+NK2 cells in newly-diagnosed asthmatics vs. asthmatics UT and controls.
In serum we found elevated levels of IL-1β in newly-diagnosed asthmatics vs. asthmatics UT Newly-diagnosed asthmatics showed higher IL-8 levels compared to asthmatics UT and controls. We showed higher IL-5 levels in newly-diagnosed asthmatics vs. controls. Higher IL-13 levels were detected in newly-diagnosed asthmatics vs. other groups and also in controls vs. patients with asthma UT. IL-10 and IL-12 levels were decreased in newly-diagnosed asthmatics vs. controls. IL-2 levels were low in both asthmatics vs. controls.
Conclusion: In order to use NK cells as a therapeutic target, a strategy must be established to regulate its cytokine secretion functions with respect to their role of these cells in each disease.

Keywords: Asthma, flow cytometry, natural killer cells cytokines

Ast�ml� Hastalarda Do�al �ld�r�c� (NK) H�cre �ntrasitoplazmik ve Plazma Sitokin Seviyeleri

Nilg�n Akdeniz¹, Esin �etin¹, Gaye Erten Yurdag�l¹, Vuslat Y�lmaz², Bilun Gemicioglu³, G�nnur Deniz¹
¹�stanbul �niversitesi, Aziz Sancar Deneysel T�p Ara�t�rma Enstit�s�, �mm�noloji Anabilim Dal�, �stanbul, T�rkiye
²�stanbul �niversitesi, Aziz Sancar Deneysel T�p Ara�t�rma Enstit�s�, Sinirbilim Anabilim Dal�, �stanbul, T�rkiye
³�stanbul �niversitesi Cerrahpa�a, Cerrahpa�a T�p Fak�ltesi, G��s Hastal�klar� Anabilim Dal�, �stanbul, T�rkiye

Ama�: Do�al �ld�r�c� h�creler, kronik inflamatuvar havayolu hastal�klar�n�n patogenezinde imm�nomod�lat�r rol oynamaktad�r. NK h�creleri, tip 2 sitokinlerin �retimini art�rarak alerjik havayolu iltihab�na neden olabilmektedir.
Gere� ve Y�ntem: Yeni te�his edilmi� (YT) ast�m hastalar�nda, tedavi alt�ndaki (TA) ast�ml� hasta ve kontrol �rneklerinde, NK h�cre IL-13, IL-4, IFNγ ve IL-10'un intrasitoplazmik sitokin seviyeleri ve serumda IFN-γ, TNF-α, IL-2, IL-8, IL-4, IL-5, IL-6, IL-17, IL12, IL-13, IL-1β ve IL-10 seviyelerini akan h�cre �l�er ve ProcartaPlex multipleks kiti kullan�larak de�erlendirilmi�tir.
Bulgular: IFN-γ+ NK1 h�creleri her iki hasta grubunda da azalm��t�r, her iki ast�ml� grup kar��la�t�r�ld��nda IFN-γ+ NK1 h�creleri TA ast�ml�larda daha y�ksektir. NK h�crelerinin h�crei�i IL-4, kontrollere g�re her iki hasta grubunda daha y�ksektir. IL-10+ NK h�creleri, kontrollere g�re her iki hasta grubunda daha d��kt�r. TA ast�ml� ve kontrollere g�re, YT ast�ml�larda IL-13+ NK2 h�crelerinin say�s�n�n artt�� g�zlenmi�tir.
Serumda, yeni tan�l� ast�ml�larda TA hastalara kar�� y�ksek IL-1β seviyeleri bulunmu�tur. Yeni te�his edilmi� ast�ml�lar, ast�ml�lar UT ve kontrollere k�yasla daha y�ksek IL-8 seviyeleri g�stermi�tir. Yeni te�hisli ast�ml�larda kontrollere g�re daha y�ksek IL-5 seviyeleri saptanm��t�r. Yeni te�hisli ast�ml�larda di�er gruplara g�re ve ayr�ca TA ast�ml� hastalara k�yasla kontrollerde daha y�ksek IL-13 seviyeleri tespit edilmi�tir. IL-10 ve IL-12 seviyeleri, yeni te�hi�li ast�ml�larda kontrollere g�re azalm��t�r. IL-2 seviyeleri hem ast�ml�larda hem kontrollerde d��k saptanm��t�r.
Sonu�: NK h�crelerini terap�tik bir hedef olarak kullanmak i�in, her hastal�kta bu h�crelerin rol�ne g�re sitokin salg�lama fonksiyonlar�n� d�zenlemek amac�yla bir strateji olu�turulmal�d�r.

Anahtar Kelimeler: Ast�m, akan h�cre �l�er, do�al �ld�r�c� h�cre sitokinleri

Corresponding Author: G�nnur Deniz, T�rkiye
Manuscript Language: English

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Intracytoplasmic and Plasma Cytokine Levels of Natural Killer Cells in Patients with Asthma

Ast�ml� Hastalarda Do�al �ld�r�c� (NK) H�cre �ntrasitoplazmik ve Plazma Sitokin Seviyeleri