Naslov
Modulation of NK cell phenotype by deletion of ST2 receptor

Autori
Jovanovic, Ivan ; Juranic Lisnic, Vanda ; Radosavljevic, Gordana ; Mitrovic, Maja ; Arsenijevic, Nebojsa ; Jonjic, Stipan ; Lukic, Miodrag

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
NK2010 - 12th Meeting of the Society for Natural immunity

Mjesto i datum
Cavtat, Hrvatska, 11.09.2010. - 15.09.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
nk cells; tumor; st2

Sažetak
ST2 molecule is a member of the Interleukin- 1Receptor (IL-1R) family. It is expressed on Th-2 T cells and NK cells and its ligand is a member of IL-1 family, IL-33. Although the role of ST2 in adaptive immunity is well understood, little is known about its function in NK cell physiology. Our previous experiments provided evidence that deletion of ST2 signaling may enhance anti-tumor response in a model of primary breast cancer with pulmonary and liver metastases, and modulated cellular make up of draining lymph node, production of pro- inflammatory cytokines, and cytotoxic activity of lymphoid cells. Objective: The aim of our study was to estimate the number and phenotype of NK cells as potential effector cells in observed antitumor activity in ST2 deficient mice (ST2-/-) in comparison to wild type (WT) BALB/C mice. Methods: Female mice, 11 weeks old, were used in the experiments. Single- cell suspensions of spleens and inguinal lymph nodes were obtained and cells incubated with monoclonal antibodies specific for mouse CD3, CD19, NKp46, NKG2D, CD27, CD11b, CD69, and KLRG1 or isotype- matched controls and analyzed by FACSAria Flow cytometer. Results: There was no significant difference in the total number of NK cells in the spleen and lymph nodes. However, ST2-/- mice have lower percentage of total CD3+-NK p46+ cells in the spleen (p=0, 01). There was significantly higher percentage of highly active, cytokine producing cytotoxic and tumoricidal CD27highCD11bhigh NK cells (p=0, 05), as well as percentage of immature CD27highCD11blow NK cells (p=0, 006). ST2-/- mice also have higher percentage of activated CD69+ NK cells (p=0, 041) and lower percentage of KLRG1+ NK cells (p=0, 011). Similar findings are observed in lymph nodes. Interestingly, NKG2D was downregulated in both ST2-/- and wild type mice after tumor inoculation suggesting that it might not be involved in observed enhanced antitumor activity in ST2-/- mice. Conclusion: ST2 deletion enhances the number of activated highly cytotoxic and cytokine producing NK cells indicating regulatory role of IL-33 ST2 signaling pathway in NK physiology. Observed enhancement of antitumor response in ST2-/- may be at least in part the consequence of an NKG2D independent enhancement of NK cytotoxic activity. These data suggest that blocking of ST2 signaling may facilitate innate anti-tumor immune response and totumor resistance in a model of experimental primary breast tumor. Precise role of NK cells in enhanced anti-tumor immunity of ST2 deficient mice has still to be established.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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