Yada Ayumi, Ebihara Shin, Matsumura Kimio, Endo Shota, Maeda Tsutomu, Nakamura Akira, Akiyama Kenichi, Aiba Setsuya, Takai Toshiyuki
Department of Experimental Immunology and the CREST Program of Japan Science and Technology Corporation, Institute of Development, Aging and Cancer, Tohoku University, 980-8575, Sendai, Japan.
Cell Immunol. 2003 Sep;225(1):21-32. doi: 10.1016/j.cellimm.2003.09.008.
It is well established that activating-type Fc receptors for IgG (FcgammaR), such as FcgammaRI and FcgammaRIII, are essential for inducing inflammatory responses, whereas a unique inhibitory FcgammaR, FcgammaRIIB, inhibits intracellular signaling upon ligation of IgG-immune complexes, and can suppress inflammation and autoimmunity. Although antigen presentation is a crucial step for evoking inflammatory responses, the contribution of FcgammaRIIB to antigen presentation is controversial as to whether it regulates antigen-presenting cells (APC), particularly dendritic cells (DC), positively or negatively. In the present report, we show that the antigen targeting to both activating-type FcgammaRs, FcgammaRI/III, and inhibitory FcgammaRIIB on bone marrow-derived DC and macrophages and primary epidermal Langerhans' cells augmented T cell proliferation in vitro and elicited humoral responses upon adoptive transfer of the antigen-pulsed DC. The DC lacking FcgammaRIIB showed a reduction in IC-uptake ability and a decreased T-cell stimulation, and induced less efficient IgG production than those of DC from wild-type mice. On the other hand, the DC lacking FcR common gamma subunit, which only expresses FcgammaRIIB, showed significant up-regulations of IC-uptake, T-cell proliferation, and IgG production compared to those of FcgammaR null DC, demonstrating a positive regulation of FcgammaRIIB for the efficient antigen presentation of IgG-complexed antigens. These results support the therapeutic benefits of antigen-targeting to FcgammaR on APC in the various inflammatory disorders.
众所周知，IgG的激活型Fc受体（FcγR），如FcγRI和FcγRIII，对于诱导炎症反应至关重要，而独特的抑制性FcγR即FcγRIIB，在IgG免疫复合物结合后可抑制细胞内信号传导，并能抑制炎症和自身免疫。尽管抗原呈递是引发炎症反应的关键步骤，但FcγRIIB在抗原呈递中的作用存在争议，即它对抗原呈递细胞（APC），特别是树突状细胞（DC）的调节是正向还是负向。在本报告中，我们表明，靶向骨髓来源的DC、巨噬细胞和原发性表皮朗格汉斯细胞上的激活型FcγR（FcγRI/III）和抑制性FcγRIIB的抗原，在体外增强了T细胞增殖，并在抗原脉冲DC过继转移后引发了体液反应。缺乏FcγRIIB的DC显示出IC摄取能力降低和T细胞刺激减少，并且与野生型小鼠的DC相比，诱导产生的IgG效率更低。另一方面，缺乏FcR共同γ亚基（仅表达FcγRIIB）的DC与FcγR缺失的DC相比，显示出IC摄取、T细胞增殖和IgG产生的显著上调，表明FcγRIIB对IgG复合抗原的有效抗原呈递具有正向调节作用。这些结果支持了在各种炎症性疾病中，抗原靶向APC上的FcγR具有治疗益处。
