Immune receptor signaling, aging, and autoimmunity

被引:56
作者
Hasler, P
Zouali, M
机构
[1] INSERM, U430, F-75006 Paris, France
[2] Kantonsspital Aarau, Rheumaklin, Aarau, Switzerland
关键词
autoimmunity; aging; immune receptor; signaling; elderly;
D O I
10.1016/j.cellimm.2005.04.012
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
With advancing age, the immune system undergoes changes that predispose to autoimmune reactivity. Aging reduces the efficiency of physical barriers, decreasing protection against invasive pathogens, and exposing previously hidden antigens in the body's own tissues. Self-antigens acquire alterations that increase their immunogenicity. In addition, the ability of innate immunity to eliminate infectious agents deteriorates, resulting in inappropriate persistence of immune stimulation and antigen levels exceeding the threshold for the activation of B or T cells. B cell turnover is reduced and numbers of naive T cells decline to the advantage of increasing numbers of memory T cells. In parallel, the loss of co-stimulatory T cell molecules may increase reactivity of T cells, and render them less susceptible to downregulation. Since optimal immune reactivity requires a tight balance of transduction pathways in both T and B lymphocytes, and because these pathways are altered in systemic autoimmune diseases, we would like to propose that, with age, alterations of the immune receptor signaling machinery underlie the higher incidence of autoimmune phenomena in the elderly. Consistently, aging is associated with alterations in several components of the signaling complex in B cells, memory and naive T cells, and a reduced activation of several lipid rafts-associated proteins. Because the coincidence of autoimmune disease with other ailments increases the burden of disease and limits therapeutic options in the aged, further investigation of these pathways in the elderly represents a challenge that will need to be addressed in order to devise effective preventive and therapeutic interventions. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:102 / 108
页数:7
相关论文
共 87 条
[1]  
Allison MED, 2000, EUR J IMMUNOL, V30, P2881, DOI 10.1002/1521-4141(200010)30:10<2881::AID-IMMU2881>3.0.CO
[2]  
2-9
[3]   Reduction in DNA binding activity of the transcription factor Pax-5a in B lymphocytes of aged mice [J].
Anspach, J ;
Poulsen, G ;
Kaattari, I ;
Pollock, R ;
Zwollo, P .
JOURNAL OF IMMUNOLOGY, 2001, 166 (04) :2617-2626
[4]   Thymic involution in aging [J].
Aspinall, R ;
Andrew, D .
JOURNAL OF CLINICAL IMMUNOLOGY, 2000, 20 (04) :250-256
[5]   Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: Role of peroxynitrite [J].
Beharka, AA ;
Wu, DY ;
Serafini, M ;
Meydani, SN .
FREE RADICAL BIOLOGY AND MEDICINE, 2002, 32 (06) :503-511
[6]   Neutrophil migration, oxidative metabolism, and adhesion in elderly and young subjects [J].
Biasi, D ;
Carletto, A ;
Dellagnola, C ;
Caramaschi, P ;
Montesanti, F ;
Zavateri, G ;
Zeminian, S ;
Bellavite, P ;
Bambara, LM .
INFLAMMATION, 1996, 20 (06) :673-681
[7]   Age-related inflammatory cytokines and disease [J].
Brüünsgaard, H ;
Pedersen, BK .
IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA, 2003, 23 (01) :15-+
[8]   Racial differences in the prevalence of monoclonal gammopathy in a community-based sample of the elderly [J].
Cohen, HJ ;
Crawford, J ;
Rao, MK ;
Pieper, CF ;
Currie, MS .
AMERICAN JOURNAL OF MEDICINE, 1998, 104 (05) :439-444
[9]   POLYMORPHONUCLEAR FUNCTIONS AND AGING IN HUMANS [J].
CORBERAND, J ;
NGYEN, F ;
LAHARRAGUE, P ;
FONTANILLES, AM ;
GLEYZES, B ;
GYRARD, E ;
SENEGAS, C .
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 1981, 29 (09) :391-397
[10]  
Crawford R M, 1994, Immunol Ser, V60, P29