Impaired Treg-DC interactions contribute to autoimmunity in leukocyte adhesion deficiency type 1.
Impaired Treg-DC interactions contribute to autoimmunity in leukocyte adhesion deficiency type 1.
复制标题
DOI：
10.1172/jci.insight.162580
复制
发表时间：
2022-12-22
期刊：
影响因子：
8
通讯作者：
Grabbe, Stephan
中科院分区：
文献类型：
--
作者：
Klaus, Tanja;Wilson, Alicia S.;Vicari, Elisabeth;Hadaschik, Eva;Klein, Matthias;Helbich, Sara Salome Clara;Kamenjarin, Nadine;Hodapp, Katrin;Schunke, Jenny;Haist, Maximilian;Butsch, Florian;Probst, Hans Christian;Enk, Alexander H.;Mahnke, Karsten;Waisman, Ari;Bednarczyk, Monika;Bros, Matthias;Bopp, Tobias;Grabbe, Stephan
白细胞粘附缺陷1型（LAD-1）是一种罕见的疾病，由编码β2-整合素家族（CD 18）共同β链的基因突变引起。最突出的临床症状是严重的白细胞增多和对感染的高度易感性。LAD-1患者容易发展为自身免疫性疾病，但导致免疫缺陷和自身免疫共存的分子和细胞机制仍未解决。已知CD 4 + FOXP 3 + Treg在预防自身免疫中的重要作用。为了理解Treg在LAD-1发展和自身免疫表现中的作用，我们产生了Treg上特异性缺乏CD 18（CD 18Foxp 3）的小鼠，导致LFA-1表达缺陷。在这里，我们证明了LFA-1对Treg的关键作用，通过修饰T细胞-DC相互作用和CD 4 + T细胞活化来维持免疫稳态。Treg特异性CD 18缺失并不损害Treg向淋巴外器官的迁移，但它导致Treg与DC的相互作用缩短。在体内，CD 18Foxp 3小鼠在淋巴器官中发生自发性增生，并在皮肤和多个内脏器官中发生弥漫性炎症。因此，Treg上的LFA-1是维持免疫稳态所必需的。
Leukocyte adhesion deficiency type 1 (LAD-1) is a rare disease resulting from mutations in the gene encoding for the common β-chain of the β2-integrin family (CD18). The most prominent clinical symptoms are profound leukocytosis and high susceptibility to infections. Patients with LAD-1 are prone to develop autoimmune diseases, but the molecular and cellular mechanisms that result in coexisting immunodeficiency and autoimmunity are still unresolved. CD4+FOXP3+ Treg are known for their essential role in preventing autoimmunity. To understand the role of Treg in LAD-1 development and manifestation of autoimmunity, we generated mice specifically lacking CD18 on Treg (CD18Foxp3), resulting in defective LFA-1 expression. Here, we demonstrate a crucial role of LFA-1 on Treg to maintain immune homeostasis by modifying T cell–DC interactions and CD4+ T cell activation. Treg-specific CD18 deletion did not impair Treg migration into extralymphatic organs, but it resulted in shorter interactions of Treg with DC. In vivo, CD18Foxp3 mice developed spontaneous hyperplasia in lymphatic organs and diffuse inflammation of the skin and in multiple internal organs. Thus, LFA-1 on Treg is required for the maintenance of immune homeostasis.
登录
查看更多内容
影响因子：
8.6
作者：
De Rose, Domenico Umberto;Giliani, Silvia;Badolato, Raffaele
通讯作者：
Badolato, Raffaele
影响因子：
4.4
作者：
Deane, James A.;Abeynaike, Latasha D.;Hickey, Michael J.
通讯作者：
Hickey, Michael J.
影响因子：
4.4
作者：
Graf, Beth;Bushnell, Timothy;Miller, Jim
通讯作者：
Miller, Jim
DOI：
10.1073/pnas.93.5.2116
发表时间：
1996-03-05
影响因子：
11.1
作者：
Bullard, DC;ScharffetterKochanek, K;Beaudet, AL
通讯作者：
Beaudet, AL
影响因子：
15.9
作者：
Grabbe, S;Varga, G;Scharffetter-Kochanek, K
通讯作者：
Scharffetter-Kochanek, K