Role of phosphoinositide 3-kinase signaling in autoimmunity

被引:15
作者
Oak, Jean S. [1 ]
Fruman, David A. [1 ]
机构
[1] Univ Calif Irvine, Ctr Immunol, Dept Mol Biol & Biochem, Irvine, CA 92697 USA
基金
美国国家卫生研究院;
关键词
phosphoinositide 3-kinase ( PI3K); T cells; autoimmunity; signal transduction;
D O I
10.1080/08916930701464780
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 [免疫学];
摘要
Activation of the phosphoinositide 3-kinase (PI3K) pathway promotes proliferation and survival in many different cell types of the immune system. PI3K acts downstream of receptors that mediate proliferation and survival in T cells, and required roles for individual class I PI3K catalytic isoforms have been established. Interestingly, mice with either augmented or diminished PI3K activity in T cells develop lymphoproliferation and signs of autoimmunity. Here, we summarize our current knowledge of mouse strains with hyperactive or reduced PI3K, different isoforms of class I PI3K in T cell-mediated immunity and autoimmunity, and the therapeutic implications for modulating this pathway for treatment of various autoimmune diseases.
引用
收藏
页码:433 / 441
页数:9
相关论文
共 75 条
[1]
Essential role for the p110δ phosphoinositide 3-kinase in the allergic response [J].
Ali, K ;
Bilancio, A ;
Thomas, M ;
Pearce, W ;
Gilfillan, AM ;
Tkaczyk, C ;
Kuehn, N ;
Gray, A ;
Giddings, J ;
Peskett, E ;
Fox, R ;
Bruce, I ;
Walker, C ;
Sawyer, C ;
Okkenhaug, K ;
Finan, P ;
Vanhaesebroeck, B .
NATURE, 2004, 431 (7011) :1007-1011
[2]
Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b [J].
Bachmaier, K ;
Krawczyk, C ;
Kozieradzki, I ;
Kong, YY ;
Sasaki, T ;
Oliveira-dos-Santos, A ;
Mariathasan, S ;
Bouchard, D ;
Wakeham, A ;
Itie, A ;
Le, J ;
Ohashi, PS ;
Sarosi, I ;
Nishina, H ;
Lipkowitz, S ;
Penninger, JM .
NATURE, 2000, 403 (6766) :211-216
[3]
Class IB-phosphatidylinositol 3-kinase (PI3K) deficiency ameliorates IA-PI3K-induced systemic lupus but not T cell invasion [J].
Barber, DF ;
Bartolomé, A ;
Hernandez, C ;
Flores, JM ;
Fernandez-Arias, C ;
Rodríguez-Borlado, L ;
Hirsch, E ;
Wymann, M ;
Balomenos, D ;
Carrera, AC .
JOURNAL OF IMMUNOLOGY, 2006, 176 (01) :589-593
[4]
PI3Kγ inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus [J].
Barber, DF ;
Bartolomé, A ;
Hernandez, C ;
Flores, JM ;
Redondo, C ;
Fernandez-Arias, C ;
Camps, M ;
Ruckle, T ;
Schwarz, MK ;
Rodríguez, S ;
Martinez-A, C ;
Balomenos, D ;
Rommel, C ;
Carrera, AC .
NATURE MEDICINE, 2005, 11 (09) :933-935
[5]
THE ITK RECEPTOR TYROSINE KINASE IS EXPRESSED IN PRE-B LYMPHOCYTES AND CEREBRAL NEURONS AND USES A NON-AUG TRANSLATIONAL INITIATOR [J].
BERNARDS, A ;
DELAMONTE, SM .
EMBO JOURNAL, 1990, 9 (07) :2279-2287
[6]
Increased levels of interleukin-10 in saliva of Sjogrens's syndrome patients. Correlation with disease activity [J].
Bertorello, R ;
Cordone, MP ;
Contini, P ;
Rossi, P ;
Indiveri, F ;
Puppo, F ;
Cordone, G .
CLINICAL AND EXPERIMENTAL MEDICINE, 2004, 4 (03) :148-151
[7]
Key role of the p110δ isoforrn of PI3K in B-cell antigen and IL-4 receptor signaling:: comparative analysis of genetic and pharmacologic interference with p110δ function in B cells [J].
Bilancio, A ;
Okkenhaug, K ;
Camps, M ;
Emery, JL ;
Ruckle, T ;
Rommel, C ;
Vanhaesebroeck, B .
BLOOD, 2006, 107 (02) :642-650
[8]
Borlado LR, 2000, FASEB J, V14, P895
[9]
Differential regulation of B cell development, activation, and death by the Src homology 2 domain-containing 5′ inositol phosphatase (SHIP) [J].
Brauweiler, A ;
Tamir, I ;
Dal Porto, J ;
Benschop, RJ ;
Helgason, CD ;
Humphries, RK ;
Freed, JH ;
Cambier, JC .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (09) :1545-1554
[10]
T cell clones from a Sjogren's syndrome salivary gland biopsy produce high levels of IL-10 [J].
Brookes, SM ;
Cohen, SBA ;
Price, EJ ;
Webb, LMC ;
Feldmann, M ;
Maini, RN ;
Venables, PJW .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 1996, 103 (02) :268-272