Imunomodulacijska svojstva TGF-β kod bolesnika sa imunskom trombocitopenijom
Sažetak
Novi koncept patogeneze imunske trombocitopenije (ITP) fokusiran je na CD4+ T ćelije, koje se trenutno smatraju krucijalnim u stimulisanju B ćelija na produkciju anti-trombocitnih antitela. U ovoj in vitro studiji, istraživali smo profil CD4+ T ćelija obolelih od ITP i imunomodulacijske svojstva TGF-β. CD4+ T ćelije su izolovane iz mononuklearnih ćelija periferne krvi zdravih ispitanika i obolelih od ITP. Nakon kratkotrajne inkubacije, određeni su nivoi osnovnih citokina T pomoćničkih ćelija kao i broj T regulatornih ćelija (Treg). Imunomodulacijska svojstva TGF-β analizirana su praćenjem izmena u produkciji citokina IFNγ, IL-4, IL-10, IL-17 i IL-2 kao i učestalosti Treg, nakon šestodnevnog tretmana. Oboleli od ITP imali su smanjen nivo IL-4 i IL-10, povećan nivo IL-17 kao i povišen odnos IFNγ/IL-4 i IL-17/IL-10. Zanimljivo je da u šestodnevnim CD4+ T ćelijskim kulturama bez TGF-β tretmana nisu evidentirane statistički značajne razlike u nivou citokina između kontrolne i ITP grupe, osim IL-10 čiji nivo je bio značajno niži. U ITP grupi nakon TGF-β tretmana, registrovano je značajno povećanje IL-10 kao i smanjenje odnosa IL-17/IL-10 u poređenju sa ITP grupom koja nije tretirana na ovaj način. Takođe, primećena je povećana učestalost Treg. Rezultati naše studije sugerišu da oboleli od ITP pokazuju aberantnu Th1 i Th17 polarizaciju celularnog imunskog odgovora što se može korigovati stimulisanom TGF-β signalizacijom. Međutim, ispostavlja se da dugotrajna kultivacija CD4+ T ćelija nije pogodan eksperimentalni model za proučavanje imunomodulatornih svojstava u ITP usled dinamičkih fluktuacija fenotipa ovih ćelija u ex vivo uslovima.
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