Yao Chen, Zurawski Sandra M, Jarrett Elizabeth S, Chicoine Brian, Crabtree Juliet, Peterson Erik J, Zurawski Gerard, Kaplan Daniel H, Igyártó Botond Z
Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minn.
Baylor Institute for Immunology Research, Dallas, Tex.
J Allergy Clin Immunol. 2015 Nov;136(5):1387-97.e1-7. doi: 10.1016/j.jaci.2015.04.001. Epub 2015 May 9.
The contribution of individual subsets of dendritic cells (DCs) to generation of adaptive immunity is central to understanding immune homeostasis and protective immune responses.
We sought to define functions for steady-state skin DCs.
We present an approach in which we restrict antigen presentation to individual DC subsets in the skin and monitor the effects on endogenous antigen-specific CD4(+) T- and B-cell responses.
Presentation of foreign antigen by Langerhans cells (LC) in the absence of exogenous adjuvant led to a large expansion of T follicular helper (TFH) cells. This was accompanied by B-cell activation, germinal center formation, and protective antibody responses against influenza. The expansion of TFH cells and antibody responses could be elicited by both systemic and topical skin immunization. TFH cell induction was not restricted to LCs and occurred in response to antigen presentation by CD103(+) dermal DCs. CD103(+) DCs, despite inducing similar TFH responses as LCs, were less efficient in induction of germinal center B cells and humoral immune responses. We also found that skin DCs are sufficient to expand CXCR5(+) TFH cells through an IL-6- and IFN-α/β receptor-independent mechanism, but B cells were required for sustained Bcl-6(+) expression.
These data demonstrate that a major unappreciated function of skin DCs is their promotion of TFH cells and humoral immune responses that potentially represent an efficient approach for vaccination.
树突状细胞（DC）的各个亚群对适应性免疫产生的贡献对于理解免疫稳态和保护性免疫反应至关重要。
我们试图明确稳态皮肤DC的功能。
我们提出了一种方法，即限制皮肤中单个DC亚群的抗原呈递，并监测其对内源性抗原特异性CD4(+) T细胞和B细胞反应的影响。
在无外源性佐剂的情况下，朗格汉斯细胞（LC）呈递外来抗原导致T滤泡辅助（TFH）细胞大量扩增。这伴随着B细胞活化、生发中心形成以及针对流感的保护性抗体反应。TFH细胞的扩增和抗体反应可通过全身和局部皮肤免疫诱导产生。TFH细胞的诱导不限于LC，CD103(+)真皮DC呈递抗原时也会发生。尽管CD103(+) DC诱导的TFH反应与LC相似，但在诱导生发中心B细胞和体液免疫反应方面效率较低。我们还发现，皮肤DC足以通过一种不依赖IL-6和IFN-α/β受体的机制扩增CXCR5(+) TFH细胞，但持续的Bcl-6(+)表达需要B细胞。
这些数据表明，皮肤DC的一个主要未被重视的功能是促进TFH细胞和体液免疫反应，这可能是一种有效的疫苗接种方法。
