Langerhans cells require MyD88-dependent signals for Candida albicans response but not for contact hypersensitivity or migration.
Langerhans cells require MyD88-dependent signals for Candida albicans response but not for contact hypersensitivity or migration.
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DOI：
10.4049/jimmunol.1102759
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发表时间：
2012-05-01
期刊：
影响因子：
--
通讯作者：
Kaplan DH
中科院分区：
文献类型：
--
作者：
Haley K;Igyártó BZ;Ortner D;Bobr A;Kashem S;Schenten D;Kaplan DH
朗格汉斯细胞（LC）是皮肤驻留DC的一个子集，其作为未成熟DC驻留在表皮中，在表皮中它们获得抗原。LC的生命周期中的关键步骤是它们响应于各种刺激（包括半抗原的表皮致敏和C的皮肤感染）而活化为成熟DC。白色念珠菌。成熟的LC迁移到皮肤引流LN，在那里它们将抗原呈递给CD4 T细胞并调节适应性免疫应答。LC迁移被认为需要IL-1 β和IL-18对LC的直接作用。此外，TLR-配体存在于C.白念珠菌和半抗原致敏产生内源性TLR配体。两者都可以促进LC活化。我们产生了Langerin-Cre MyD88fl小鼠，其中LC对IL-1家族成员和大多数TLR-配体不敏感。半抗原致敏后和C.白色念珠菌不受影响。Langerin-Cre MyD88fl小鼠中的接触性超敏反应同样未受影响。有趣的是，在响应C。这些小鼠显示抗原特异性CD4 T细胞增殖减少和Th17亚群分化缺陷。LC上共刺激分子的表面表达是完整的，但IL-1 β、IL-6和IL-23的表达减少。因此，对MyD88依赖性信号的敏感性不是LC迁移所必需的，而是在真菌感染的情况下LC的完全激活和功能所必需的。
Langerhans cells (LC) are a subset of skin-resident DC that reside in the epidermis as immature DC where they acquire antigen. A key step in the life cycle of LC is their activation into mature DC in response to various stimuli including epicutaneous sensitization with hapten and skin infection with C. albicans. Mature LC migrate to the skin-draining LN where they present antigen to CD4 T cells and modulate the adaptive immune response. LC migration is thought to require the direct action of IL-1β and IL- 18 on LC. In addition, TLR-ligands are present in C. albicans and hapten sensitization produces endogenous TLR-ligands. Both could contribute to LC activation. We generated Langerin-Cre MyD88fl mice in which LC are insensitive to IL-1 family members and most TLR-ligands. LC migration in the steady-state, after hapten sensitization and after infection with C. albicans was unaffected. Contact hypersensitivity in Langerin-Cre MyD88fl mice was similarly unaffected. Interestingly, in response to C. albicans infection these mice displayed reduced proliferation of antigen-specific CD4 T cells and defective Th17 subset differentiation. Surface expression of co-stimulatory molecules was intact on LC but expression of IL-1β, IL-6, and IL-23 was reduced. Thus, sensitivity to MyD88-dependent signals is not required for LC migration but is required for the full activation and function of LC in the setting of fungal infection.
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接触性超敏反应中朗格汉斯细胞和朗格林+真皮树突状细胞的功能冗余。
DOI：
10.1038/jid.2010.223
发表时间：
2010-12
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1001802
发表时间：
2010-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bobr A;Olvera-Gomez I;Igyarto BZ;Haley KM;Hogquist KA;Kaplan DH
通讯作者：
Kaplan DH
影响因子：
32.4
作者：
Sutterwala, FS;Ogura, Y;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
4.4
作者：
Antonopoulos, H;Cumberbatch, M;Groves, RW
通讯作者：
Groves, RW
影响因子：
6.5
作者：
Watanabe, Hideki;Gaide, Olivier;French, Lars E.
通讯作者：
French, Lars E.