Wadsworth Center, New York State Department of Health, Albany, NY, United States.
Wadsworth Center, New York State Department of Health, Albany, NY, United States; University at Albany School of Public Health, Rensselaer, NY, United States.
Cell Immunol. 2020 Dec;358:104223. doi: 10.1016/j.cellimm.2020.104223. Epub 2020 Sep 26.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is characterized by a lack of social interaction, decreased verbal and non-verbal communication skills, and stereotyped repetitive behavior. There is strong evidence that a dysregulated immune response may influence neurodevelopment and thus may have a role in the development of ASD. This study focuses on the characterization of immune cell phenotypes in the BTBR TItpr3/J (BTBR) mouse strain, a widely used animal model for autism research. Our study demonstrated that BTBR mice have a different immune profile compared to C57BL/6J (B6) mice, which do not display ASD-like characteristics. Thymic cells of BTBR mice have more single positive (SP) CD4 and CD8 T cells and fewer double positive (DP) T cells than B6 mice. The development of T cells is increased in BTBR mice with regard to the double negative (DN4) population being much higher in BTBR mice. The spleens and blood of BTBR mice also have more T helper type 1 (Th1), T helper type 2 (Th2) and T regulatory (Treg) cells compared to B6 mice. Aire expression in the thymus and spleen of BTBR mice compared to B6 mice was equivalent and lower, respectively. The mature natural killer (NK) innate immune cell population in blood and spleen is lower in BTBR than B6 mice; NK cell development is blocked prior to the double positive (DN) CD11bCD27 stage in BTBR mice. Since BTBR mice have more CD4 T cells and elevated numbers of Th1 (T-bet) and Th2 (GATA3) cells, their low defense against pathogen may be explained by the lower number of NK cells and the significantly lower Th1 to Th2 ratio. The elevated number of plasma cells and autoantibodies of BTBR mice may be due to less presence and function of splenic AIRE.
自闭症谱系障碍（ASD）是一种复杂的神经发育障碍，其特征是缺乏社交互动、语言和非语言沟通能力下降以及刻板重复行为。有强有力的证据表明，免疫反应失调可能会影响神经发育，因此可能在 ASD 的发展中起作用。本研究专注于 BTBR TItpr3/J（BTBR）小鼠品系中免疫细胞表型的特征，BTBR 是自闭症研究中广泛使用的动物模型。我们的研究表明，与不表现出自闭症特征的 C57BL/6J（B6）小鼠相比，BTBR 小鼠具有不同的免疫特征。BTBR 小鼠的胸腺细胞具有更多的单阳性（SP）CD4 和 CD8 T 细胞，而双阳性（DP）T 细胞较少。BTBR 小鼠的 T 细胞发育增加，双阴性（DN4）群体在 BTBR 小鼠中要高得多。BTBR 小鼠的脾脏和血液中的 T 辅助细胞 1（Th1）、T 辅助细胞 2（Th2）和 T 调节（Treg）细胞也比 B6 小鼠多。与 B6 小鼠相比，BTBR 小鼠的胸腺和脾脏中的 AIRE 表达相当且较低。BTBR 小鼠血液和脾脏中的成熟自然杀伤（NK）固有免疫细胞群体比 B6 小鼠低；BTBR 小鼠的 NK 细胞发育在双阳性（DN）CD11bCD27 阶段之前受阻。由于 BTBR 小鼠具有更多的 CD4 T 细胞和升高的 Th1（T-bet）和 Th2（GATA3）细胞数量，其对病原体的防御能力较低可能是由于 NK 细胞数量减少和 Th1 与 Th2 比值显著降低所致。BTBR 小鼠的浆细胞和自身抗体数量增加可能是由于脾脏 AIRE 的存在和功能减少所致。
