Role of relevant immune-modulators and cytokines in hepatocellular carcinoma and premalignant hepatic lesions
WORLD JOURNAL OF GASTROENTEROLOGY
Authors: Zekri, Abdel-Rahman N.; El Deeb, Somaya; Bahnassy, Abeer A.; Badr, Abeer M.; Abdellateif, Mona S.; Esmat, Gamal; Salama, Hosny; Mohanad, Marwa; El-dien, Ahmed Esam; Rabah, Shimaa; Abd Elkader, Assmaa
Abstract
AIM to assess the levels of different immune modulators in patients with hepatocellular carcinoma (HCC), in relation to other hepatic diseases. METHODS Eighty-eight patients were included in the current study and represented patients with HCC (20), liver cirrhosis (28) and chronic hepatitis (CH; 25), and normal controls (NC; 15). Peripheral blood was isolated for immunophenotyping of active myeloid dendritic cells (mDCs; CD1c and CD40), mature inactive myeloid cells (CD1c and HLA), active plasmacytoid cells (pDCs; CD303 and CD40), mature inactive pDCs (CD30 and HLA), active natural killer (NK) cells (CD56 and CD161), active NK cells (CD56 and CD314) and inactive NK cells (CD56 and CD158) was done by flow cytometry. Serum levels of interleukin (IL)-2, IL-10, IL-12, IL-1 beta, interferon (IFN)-alpha, IFN-gamma and tumor necrosis factor (TNF)-alpha R2 were assessed by ELISA. RESULTS Active mDCs (CD1C+/CD40+) and inactive mDCs (CD1c+/HLA+) were significantly decreased in HCC patients in relation to NC (P < 0.001). CD40+ expression on active pDCs was decreased in HCC patients (P < 0.001), and its level was not significantly changed among other groups. Inactive pDCs (CD303+/HLA+), inactive NKs (CD56+/CD158+) and active NKs (CD56+/CD161+) were not statistically changed among the four groups studied; however, the latter was increased in CH (P < 0.05). NKG2D was statistically decreased in HCC, CH and cirrhosis (P < 0.001), and it was not expressed in 63% (12/20) of HCC patients. There was significant decrease of IL-2, IFN-alpha and IFN-gamma (P < 0.001), and a significant increase in IL-10, IL-1 beta, and TNF-alpha R2 (P < 0.01, P < 0.001 and P < 0.001; respectively) in HCC patients. There was inverted correlation between IL-12 and IL-1 beta in HCC (r = -0.565, P < 0.01), with a strong correlation between pDCs (CD303+/CD40+) and NKs (CD56+/CD161+; r = 0.512, P < 0.05) as well as inactive mDCs (CD1c+/HLA+) and inactive NK cells (CD56+/CD158+; r = 0.945, P < 0.001). CONCLUSION NKG2D, CD40, IL-2 and IL-10 are important modulators in the development and progression of HCC.
Acute aerobic exercise induces a preferential mobilisation of plasmacytoid dendritic cells into the peripheral blood in man
PHYSIOLOGY & BEHAVIOR
Authors: Brown, Frankie F.; Campbell, John P.; Wadley, Alex J.; Fisher, James P.; Aldred, Sarah; Turner, James E.
Abstract
Dendritic cells (DCs) are important sentinel cells of the immune system responsible for presenting antigen to T cells. Exercise is known to cause an acute and transient increase in the frequency of DCs in the bloodstream in humans, yet there are contradictory findings in the literature regarding the phenotypic composition of DCs mobilised during exercise, which may have implications for immune regulation and health. Accordingly, we sought to investigate the composition of DC sub-populations mobilised in response to acute aerobic exercise. Nine healthy males (age, 21.9 +/- 3.6 years; height, 177.8 +/- 5.4 cm; body mass, 78.9 +/- 10.8 kg; body mass index, 24.9 +/- 3.3 kg.m(2); VO2 (MAX), 41.5 +/- 5.1 mL.kg.min(-1)) cycled for 20 min at 80% VO2 (MAX). Blood was sampled at baseline, during the final minute of exercise and 30 min later. Using flow cytometry, total DCs were defined as Lineage - (CD3, CD19, CD20, CD14, CD56) HLA-DR+ and subsequently identified as plasmacytoid DCs (CD303+) and myeloid DCs (CD303-). Myeloid DCs were analysed for expression of CD1c and CD141 to yield four sub-populations; CD1c-CD141+; CD1c+CD141+; CD1c+CD141- and CD1c-CD141-. Expression of CD205 was also analysed on all DC sub-populations to identify DCs capable of recognising apoptotic and necrotic cells. Total DCs increased by 150% during exercise (F-(1,F-10) = 60; p < 0.05, eta(2) = 0.9). Plasmacytoid DCs mobilised to a greater magnitude than myeloid DCs (195 +/- 131% vs. 131 +/- 100%; p < 0.05). Among myeloid DCs, CD1c-CD141- cells showed the largest exercise-induced mobilisation (167 +/- 122%), with a stepwise pattern observed among the remaining sub-populations: CD1c+CD141- (79 +/- 50%), followed by CD1c+CD141+ (44 +/- 41%), with the smallest response shown by CD1c-CD141+ cells (23 +/- 54%) (p < 0.05). Among myeloid DCs, CD205- cells were the most exercise responsive. All DC subsets returned to resting levels within 30 min of exercise cessation. These results show that there is a preferential mobilisation of plasmacytoid DCs during exercise. Given the functional repertoire of plasmacytoid DCs, which includes the production of interferon against viral and bacterial pathogens, these findings indicate that exercise may augment immune-surveillance by preferentially mobilising effector cells; these findings have general implications for the promotion of exercise for health, and specifically for the optimisation of DC harvest for cancer immunotherapy.