Intrinsic autoimmune capacities of hematopoietic cells from female New Zealand hybrid mice.
Intrinsic autoimmune capacities of hematopoietic cells from female New Zealand hybrid mice.
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DOI：
10.1038/gene.2014.2
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发表时间：
2014-04
影响因子：
5
通讯作者：
Jorgensen, T. N.
中科院分区：
文献类型：
--
作者：
David, A.;Trigunaite, A.;MacLeod, M. K.;Johnson, A. C.;Marrack, P.;Jorgensen, T. N.
大多数全身性自身免疫性疾病在女性中发生的频率高于男性。这在干燥综合征、系统性红斑狼疮（SLE）和甲状腺自身免疫中尤为明显，其中女性与男性的比例范围为20：1至8：1。我们对SLE病因学的理解意味着遗传、环境因素和性激素的重要作用，但每一个因素的相对重要性仍然未知。使用新西兰杂交小鼠模型系统的SLE，我们在这里提出了一个新的胎肝嵌合体为基础的系统中，我们可以分离的免疫系统基因的影响，在体内的性激素。我们发现，雌性造血细胞表达一种内在的能力，驱动狼疮样疾病在男性和女性受体小鼠，这表明这种能力是激素无关的。特别地，只有具有雌性造血系统的嵌合小鼠显示出生殖中心B细胞、记忆B细胞和浆细胞的数量显著增加，随后对核组分的耐受性自发丧失，因此血清抗核自身抗体升高。注意到睾酮的保护作用与疾病发作有关，而不是疾病发生率。因此，在女性造血系统内编码的遗传因子可以有效地驱动狼疮样疾病，即使在男性受体中。
Most systemic autoimmune diseases occur more frequently in females than in males. This is particularly evident in Sjögren’s Syndrome, Systemic Lupus Erythromatosis (SLE) and thyroid autoimmunity, where the ratio of females to males ranges from 20:1 to 8:1. Our understanding of the etiology of SLE implies important roles for genetics, environmental factors and sex hormones, but the relative significance of each remains unknown. Using the New Zealand hybrid mouse model system of SLE we present here a new fetal liver chimera-based system in which we can segregate effects of immune system genes from that of sex hormones in vivo. We show that female hematopoietic cells express an intrinsic capacity to drive lupus-like disease in both male and female recipient mice, suggesting that this capacity is hormone independent. Particularly, only chimeric mice with a female hematopoietic system showed significantly increased numbers of germinal center B cells, memory B cells and plasma cells followed by a spontaneous loss of tolerance to nuclear components and hence elevated serum anti-nuclear autoantibodies. A protective effect of testosterone was noted with regards to disease onset, not disease incidence. Thus, genetic factors encoded within the female hematopoietic system can effectively drive lupus-like disease even in male recipients.
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影响因子：
3.7
作者：
Chang, Nan-Hua;Cheung, Yui-Ho;Wither, Joan
通讯作者：
Wither, Joan
DOI：
10.1084/jem.20101715
发表时间：
2011-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kelly-Scumpia KM;Scumpia PO;Weinstein JS;Delano MJ;Cuenca AG;Nacionales DC;Wynn JL;Lee PY;Kumagai Y;Efron PA;Akira S;Wasserfall C;Atkinson MA;Moldawer LL
通讯作者：
Moldawer LL
影响因子：
9.1
作者：
Chauhan, Sudhir Kumar;Singh, Vikas Vikram;Rai, Geeta
通讯作者：
Rai, Geeta
影响因子：
30.5
作者：
Buerckstuemmer, Tilmann;Baumann, Christoph;Superti-Furga, Giulio
通讯作者：
Superti-Furga, Giulio
影响因子：
5
作者：
Bynote, K. K.;Hackenberg, J. M.;Gould, K. A.
通讯作者：
Gould, K. A.