SOCS5 is expressed in primary B and T lymphoid cells but is dispensable for lymphocyte production and function

被引:60
作者
Brender, C
Columbus, R
Metcalf, D
Handman, E
Starr, R
Huntington, N
Tarlinton, D
Odum, N
Nicholson, SE
Nicola, NA
Hilton, DJ
Alexander, WS
机构
[1] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
[2] Univ Copenhagen, Inst Med Microbiol & Immunol, Copenhagen, Denmark
[3] Univ Copenhagen, Inst Mol Biol, Copenhagen, Denmark
关键词
D O I
10.1128/MCB.24.13.6094-6103.2004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Suppressors of cytokine signaling (SOCSs) are key regulators of cytokine-induced responses in hematopoietic as well as nonhematopoietic cells. SOCS1 and SOCS3 have been shown to modulate T-cell responses, whereas the roles of other SOCS family members in the regulation of lymphocyte function are less clear. Here, we report the generation of mice with a targeted disruption of the Socs5 gene. Socs5(-/-) mice were born in a normal Mendelian ratio and were healthy and fertile. We found that SOCS5 is expressed in primary B and T cells in wild-type mice. However, no abnormalities in the lymphocyte compartment were seen in SOCS5-deficient mice. We examined antigen- and cytokine-induced proliferative responses in B and T cells in the absence of SOCS5 and found no deviations from the responses seen in wild-type cells. Because SOCS5 has been implicated in Th1 differentiation, we also investigated the importance of SOCS5 in T helper cell responses. Unexpectedly, SOCS5-deficient CD4 T cells showed no abnormalities in Th1/Th2 differentiation and Socs5(-/-) mice showed normal resistance to infection with Leishmania major. Therefore, although SOCS5 is expressed in primary B and T cells, it appears to be dispensable for the regulation of lymphocyte function.
引用
收藏
页码:6094 / 6103
页数:10
相关论文
共 47 条
[1]   Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietin receptor c-mpl [J].
Alexander, WS ;
Roberts, AW ;
Nicola, NA ;
Li, RL ;
Metcalf, D .
BLOOD, 1996, 87 (06) :2162-2170
[2]   Suppressors of cytokine signalling (SOCS) in the immune system [J].
Alexander, WS .
NATURE REVIEWS IMMUNOLOGY, 2002, 2 (06) :410-416
[3]   POINT MUTATIONS WITHIN A DIMER INTERFACE HOMOLOGY DOMAIN OF C-MPL INDUCE CONSTITUTIVE RECEPTOR ACTIVITY AND TUMORIGENICITY [J].
ALEXANDER, WS ;
METCALF, D ;
DUNN, AR .
EMBO JOURNAL, 1995, 14 (22) :5569-5578
[4]   SOCS1 is a critical inhibitor of interferon γ signaling and prevents the potentially fatal neonatal actions of this cytokine [J].
Alexander, WS ;
Starr, R ;
Fenner, JE ;
Scott, GL ;
Handman, E ;
Sprigg, NS ;
Corbin, JE ;
Cornish, AL ;
Darwiche, R ;
Owczarek, CM ;
Kay, TWH ;
Nicola, NA ;
Hertzog, PJ ;
Metcalf, D ;
Hilton, DJ .
CELL, 1999, 98 (05) :597-608
[5]   Cutting edge: Suppressor of cytokine signaling 3 inhibits activation of NFATp [J].
Banerjee, A ;
Banks, AS ;
Nawijn, MC ;
Chen, XP ;
Rothman, PB .
JOURNAL OF IMMUNOLOGY, 2002, 168 (09) :4277-4281
[6]   Involvement of suppressor of cytokine signaling-3 as a mediator of the inhibitory effects of IL-10 on lipopolysaccharide-induced macrophage activation [J].
Berlato, C ;
Cassatella, MA ;
Kinjyo, I ;
Gatto, L ;
Yoshimura, A ;
Bazzoni, F .
JOURNAL OF IMMUNOLOGY, 2002, 168 (12) :6404-6411
[7]   Persistence of lesions in suppressor of cytokine signaling-1-deficient mice infected with Leishmania major [J].
Bullen, DVR ;
Baldwin, TM ;
Curtis, JM ;
Alexander, WS ;
Handman, E .
JOURNAL OF IMMUNOLOGY, 2003, 170 (08) :4267-4272
[8]   Suppressor of cytokine signaling-1 regulates signaling in response to interleukin-2 and other γc-dependent cytokines in peripheral T cells [J].
Cornish, AL ;
Chong, MM ;
Davey, GM ;
Darwiche, R ;
Nicola, NA ;
Hilton, DJ ;
Kay, TW ;
Starr, R ;
Alexander, WS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (25) :22755-22761
[9]   Suppressor of cytokine signaling-1 has IFn-γ-independent actions in T cell homeostasis [J].
Cornish, AL ;
Davey, GM ;
Metcalf, D ;
Purton, JF ;
Corbin, JE ;
Greenhalgh, CJ ;
Darwiche, R ;
Wu, L ;
Nicola, NA ;
Godfrey, DI ;
Heath, WR ;
Hilton, DJ ;
Alexander, WS ;
Starr, R .
JOURNAL OF IMMUNOLOGY, 2003, 170 (02) :878-886
[10]   SOCS3 negatively regulates IL-6 signaling in vivo [J].
Croker, BA ;
Krebs, DL ;
Zhang, JG ;
Wormald, S ;
Willson, TA ;
Stanley, EG ;
Robb, L ;
Greenhalgh, CJ ;
Förster, I ;
Clausen, BE ;
Nicola, NA ;
Metcalf, D ;
Hilton, DJ ;
Roberts, AW ;
Alexander, WS .
NATURE IMMUNOLOGY, 2003, 4 (06) :540-545