The difference in immune response and IL-12p35 methylation between newborns and adults

被引:9
作者
Chen, Chia-Jung [1 ]
Hou, Jia-Woei [2 ]
Chiang, Bor-Luen [3 ,4 ,5 ]
机构
[1] Sijhih Cathay Gen Hosp, Dept Pediat, Taipei, Taiwan
[2] Cathay Gen Hosp, Sect 4, Dept Pediat, Taipei 10630, Taiwan
[3] Natl Taiwan Univ, Grad Inst Immunol, Taipei 100, Taiwan
[4] Natl Taiwan Univ, Grad Inst Clin Med, Taipei, Taiwan
[5] Natl Taiwan Univ Hosp, Allergy Ctr, Taipei, Taiwan
关键词
Newborn; Interleukin-12; Methylation; CELL STIMULATORY FACTOR; NEONATAL DENDRITIC CELLS; T-CELLS; GENE-EXPRESSION; INTERFERON-GAMMA; CYTOKINE PRODUCTION; HUMAN MONOCYTES; P35; GENE; C-REL; INTERLEUKIN-12;
D O I
10.1186/s12929-014-0076-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background: The immune system of newborn is generally depressed by impaired production of Th1-cell associated cytokines, which results in increased susceptibility to intracellular pathogens and poor response to vaccinations. For avoiding abortion, the maternal and fetal immune systems tend to Th2-cell polarizing cytokines. Besides, IL-12p35 is a determining factor of the bioactivity of IL-12, which has an important role in the Th1 response. Recently methylated DNA is known to associate to inhibit transcription. Therefore, we explored the methylation status of CpG sites upstream of the coding sequence of the IL-12p35 gene to determine whether neonatal peripheral blood mononuclear cell (PBMC) synthesis lower level of IL-12 is related to methylated DNA. Results: PBMCs from adults expressed higher levels of IL-12p40 (p = 0.303) and IL-12p70 (p = 0.045) and had a strong ability to produce IL-12p35 mRNA (p = 0.01). However, there was no difference in the methylation status of CpG sites in the promoter of IL-12p35 between adults and newborns. Conclusions: We found that PBMC synthesis of bioactive IL-12p70 was significantly impaired in the neonatal period, potentially though a reduction in IL-12p35 production. The reeducation in IL-12p35 production might not be due to methylation of the promoter gene. But, the impairment of IL-12p35 expression during the neonatal period might be caused by other epigenetic regulation occurs in the chromatin level.
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页数:8
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[1]   The generation of th memory in neonates versus adults: Prolonged primary Th2 effector function and impaired development of Th1 memory effector function in murine neonates [J].
Adkins, P ;
Bu, YR ;
Guevara, P .
JOURNAL OF IMMUNOLOGY, 2001, 166 (02) :918-925
[2]   Defective IL2 gene expression in newborn is accompanied with impaired tyrosine-phosphorylation in T cells [J].
Ansart-Pirenne, H ;
Soulimani, N ;
Tartour, E ;
Blot, P ;
Sterkers, G .
PEDIATRIC RESEARCH, 1999, 45 (03) :409-413
[3]   Mechanisms of disease: The effect of infections on susceptibility to autoimmune and allergic diseases [J].
Bach, JF .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 347 (12) :911-920
[4]   Skewed pattern of Toll-like receptor 4-mediated cytokine production in human neonatal blood: Low LPS-induced IL-12p70 and high IL-10 persist throughout the first month of life [J].
Belderbos, M. E. ;
van Bleek, G. M. ;
Levy, O. ;
Blanken, M. O. ;
Houben, M. L. ;
Schuijff, L. ;
Kimpen, J. L. L. ;
Bont, L. .
CLINICAL IMMUNOLOGY, 2009, 133 (02) :228-237
[5]   Neonatal Plasma Polarizes TLR4-Mediated Cytokine Responses towards Low IL-12p70 and High IL-10 Production via Distinct Factors [J].
Belderbos, Mirjam E. ;
Levy, Ofer ;
Stalpers, Femke ;
Kimpen, Jan L. ;
Meyaard, Linde ;
Bont, Louis .
PLOS ONE, 2012, 7 (03)
[6]   Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens [J].
Chelvarajan, RL ;
Collins, SM ;
Doubinskaia, IE ;
Goes, S ;
Van Willigen, J ;
Flanagan, D ;
de Villiers, WJS ;
Bryson, JS ;
Bondada, S .
JOURNAL OF LEUKOCYTE BIOLOGY, 2004, 75 (06) :982-994
[7]   Maturation of human neonatal CD4+ and CD8+ T lymphocytes into Th1/Th2 effectors [J].
Delespesse, G ;
Yang, LP ;
Ohshima, Y ;
Demeure, C ;
Shu, U ;
Byun, DG ;
Sarfati, M .
VACCINE, 1998, 16 (14-15) :1415-1419
[8]   Microbial recognition via toll-like receptor-dependent and -independent pathways determines the cytokine response of murine dendritic cell subsets to CD40 triggering [J].
Edwards, AD ;
Manickasingham, SP ;
Spörri, R ;
Diebold, SS ;
Schulz, O ;
Sher, A ;
Kaisho, T ;
Akira, S ;
Sousa, CRE .
JOURNAL OF IMMUNOLOGY, 2002, 169 (07) :3652-3660
[9]  
Firth Matthew A., 2005, Animal Health Research Reviews, V6, P143, DOI 10.1079/AHR2005107
[10]   The interleukin-12/interleukin-12-receptor system: Role in normal and pathologic immune responses [J].
Gately, MK ;
Renzetti, LM ;
Magram, J ;
Stern, AS ;
Adorini, L ;
Gubler, U ;
Presky, DH .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :495-521