SPARC coordinates extracellular matrix remodeling and efficient recruitment to and migration of antigen-specific T cells in the brain following infection.
SPARC coordinates extracellular matrix remodeling and efficient recruitment to and migration of antigen-specific T cells in the brain following infection.
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DOI：
10.1038/s41598-021-83952-0
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发表时间：
2021-02-25
影响因子：
4.6
通讯作者：
Wilson EH
中科院分区：
文献类型：
--
作者：
McGovern KE;Nance JP;David CN;Harrison RES;Noor S;Worth D;Landrith TA;Obenaus A;Carson MJ;Morikis D;Wilson EH
中枢神经系统（CNS）损伤和感染可导致大脑中深刻的组织重塑，但其机制和目的尚不清楚。原生动物寄生虫弓形虫感染会导致脑实质慢性感染和炎症。寄生虫复制的控制需要产生 IFNγ 的 T 细胞持续存在，以保持弓形虫缓慢复制的包囊形式。在感染过程中，通过多光子显微镜显示，大脑中形成了细胞外基质纤维网络。这些结构的起源和组成尚不清楚，但已观察到这些纤维可作为 T 细胞迁移的基质。在这项研究中，我们发现，在额叶皮层感染的早期阶段，细胞外基质（ECM）重塑的关键调节剂——富含半胱氨酸的酸性分泌蛋白（SPARC）在大脑中表达上调。在缺乏 SPARC 的情况下，纤维网络减少且无序、寄生虫负担增加以及进入大脑的抗原特异性 T 细胞减少，表明 SPARC 在 T 细胞招募到大脑和在大脑内迁移中发挥着作用。我们还报道 SPARC 可以直接结合 CCR7 配体 CCL19 和 CCL21，但不能结合 CXCL10，并增强向趋化因子梯度的迁移。 T 细胞行为的测量表明组织重塑对于免疫细胞进入大脑并促进细胞运动非常重要。总之，这些数据表明 SPARC 是免疫细胞运输和进入发炎中枢神经系统的重要调节成分。
Central nervous system (CNS) injury and infection can result in profound tissue remodeling in the brain, the mechanism and purpose of which is poorly understood. Infection with the protozoan parasite Toxoplasma gondii causes chronic infection and inflammation in the brain parenchyma. Control of parasite replication requires the continuous presence of IFNγ-producing T cells to keep T. gondii in its slowly replicating cyst form. During infection, a network of extracellular matrix fibers, revealed using multiphoton microscopy, forms in the brain. The origin and composition of these structures are unknown but the fibers have been observed to act as a substrate for migrating T cells. In this study, we show a critical regulator of extracellular matrix (ECM) remodeling, Secreted Protein, Acidic, Rich in Cysteine (SPARC), is upregulated in the brain during the early phases of infection in the frontal cortex. In the absence of SPARC, a reduced and disordered fibrous network, increased parasite burden, and reduced antigen-specific T cell entry into the brain points to a role for SPARC in T cell recruitment to and migration within the brain. We also report SPARC can directly bind to CCR7 ligands CCL19 and CCL21 but not CXCL10, and enhance migration toward a chemokine gradient. Measurement of T cell behavior points to tissue remodeling being important for access of immune cells to the brain and facilitating cellular locomotion. Together, these data identify SPARC as an important regulatory component of immune cell trafficking and access to the inflamed CNS.
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影响因子：
64.8
作者：
Harris, Tajie H.;Banigan, Edward J.;Christian, David A.;Konradt, Christoph;Wojno, Elia D. Tait;Norose, Kazumi;Wilson, Emma H.;John, Beena;Weninger, Wolfgang;Luster, Andrew D.;Liu, Andrea J.;Hunter, Christopher A.
通讯作者：
Hunter, Christopher A.
影响因子：
3.1
作者：
BOHNE, W;HEESEMANN, J;GROSS, U
通讯作者：
GROSS, U
影响因子：
3
作者：
Contini, C;Cultrera, R;Delia, S
通讯作者：
Delia, S
SPARC在细胞外基质组件中的作用。
影响因子：
4.1
作者：
Bradshaw, Amy D.
通讯作者：
Bradshaw, Amy D.
影响因子：
6.4
作者：
Chlenski, A;Liu, SQ;Cohn, SL
通讯作者：
Cohn, SL