Aging impacts isolated lymphoid follicle development and function.
Aging impacts isolated lymphoid follicle development and function.
复制标题
DOI：
10.1186/1742-4933-8-1
复制
发表时间：
2011-01-07
期刊：
影响因子：
--
通讯作者：
Newberry RD
中科院分区：
文献类型：
--
作者：
McDonald KG;Leach MR;Huang C;Wang C;Newberry RD
免疫衰老是与年龄相关的保护性免疫力下降和功能障碍，导致感染、自身免疫性疾病和癌症的风险显著增加。大多数研究都集中在全身免疫系统的免疫衰老;关于衰老对肠道免疫的影响的信息是有限的。孤立淋巴滤泡（ILF）是新近发现的动态肠淋巴结构，由新生淋巴组织或隐睾（CP）响应局部炎症刺激而产生。ILF促进“稳态”反应，包括抗原特异性伊加的产生，从而在粘膜免疫保护中发挥关键作用。随着年龄的增长，ILF功能障碍可能会导致粘膜系统的免疫衰老，因此，我们研究了年轻（2个月大）和老年（2岁）小鼠ILF的表型和功能方面。我们观察到，老年小鼠ILF的数量增加，相应的CP转化为ILF的早期阶段的结构的数量增加。老年小鼠ILF的细胞组成发生改变，B淋巴细胞数量减少，T淋巴细胞数量增加。ILF T淋巴细胞群值得注意的是存在CD 4 + CD 8 αα+ T淋巴细胞，其在全身隔室中不存在。来自老年小鼠的ILF中较小的B淋巴细胞群体与CCL 20和CXCL 13的mRNA和蛋白表达降低直接相关，这两种趋化因子在将B淋巴细胞募集到ILF中起关键作用。老年小鼠血清和粪便免疫球蛋白水平升高，尽管B淋巴细胞数量减少，但老年小鼠的ILF显示伊加产生增加。免疫球蛋白库在老年小鼠中是偏斜的，并且ILF表现出与年轻和老年小鼠中的全身池相似的库使用。在这里，我们观察到ILF的发展，细胞组成，和免疫球蛋白的生产随着年龄的增长而改变，这表明ILF功能障碍有助于粘膜免疫衰老。
Immunosenescence is the age-related decline and dysfunction of protective immunity leading to a marked increase in the risk of infections, autoimmune disease, and cancer. The majority of studies have focused on immunosenescence in the systemic immune system; information concerning the effect of aging on intestinal immunity is limited. Isolated lymphoid follicles (ILFs) are newly appreciated dynamic intestinal lymphoid structures that arise from nascent lymphoid tissues, or cryptopatches (CP), in response to local inflammatory stimuli. ILFs promote "homeostatic" responses including the production of antigen-specific IgA, thus playing a key role in mucosal immune protection. ILF dysfunction with aging could contribute to immunosenescence of the mucosal system, and accordingly we examined phenotypic and functional aspects of ILFs from young (2 month old) and aged (2 year old) mice. We observed that aged mice have increased numbers of ILFs and increased numbers of structures corresponding to an early stage of CPs transforming into ILFs. The cellular composition of ILFs in aged mice is altered with a smaller B-lymphocyte population and an increased T-lymphocyte population. The ILF T-lymphocyte population is notable by the presence of CD4+ CD8αα+ T-lymphocytes, which are absent from the systemic compartment. The smaller B-lymphocyte population in ILFs from aged mice is directly correlated with decreased mRNA and protein expression of CCL20 and CXCL13, two chemokines that play crucial roles in recruiting B-lymphocytes into ILFs. Aged mice had elevated levels of serum and fecal immunoglobulins and despite the decreased B-lymphocyte population, ILFs from aged mice displayed increased IgA production. The immunoglobulin repertoire was skewed in aged mice, and ILFs demonstrated a repertoire usage similar to that of the systemic pool in both young and aged mice. Here we observed that ILF development, cellular composition, and immunoglobulin production are altered with aging suggesting that ILF dysfunction contributes to mucosal immunosenescence.
登录
查看更多内容
影响因子：
15.3
作者：
Bowman, E P;Campbell, J J;Soler, D;Dong, Z;Manlongat, N;Picarella, D;Hardy, R R;Butcher, E C
通讯作者：
Butcher, E C
影响因子：
5.5
作者：
Enioutina, EY;Visic, DM;Daynes, RA
通讯作者：
Daynes, RA
影响因子：
24.5
作者：
Fujimura, Y;Kamoi, R;Iida, M
通讯作者：
Iida, M
DOI：
10.1152/ajpgi.2001.280.4.g710
发表时间：
2001-04-01
影响因子：
4.5
作者：
Izadpanah, A;Dwinell, MB;Kagnoff, MF
通讯作者：
Kagnoff, MF
影响因子：
56.9
作者：
Fagarasan, S;Muramatsu, M;Honjo, T
通讯作者：
Honjo, T