Cantaruti Thiago Anselmo, Costa Raquel Alves, de Souza Kênia Soares, Vaz Nelson Monteiro, Carvalho Cláudia Rocha
Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Universidade Federal de São João Del Rei, Minas Gerais, Brazil.
Immunology. 2017 Jul;151(3):314-323. doi: 10.1111/imm.12732. Epub 2017 Apr 6.
Oral tolerance refers to the specific inhibition of immune responsiveness to T-cell-dependent antigens contacted through the oral route before parenteral immunization. Oral tolerance to one protein does not inhibit immune responses to other unrelated proteins, but parenteral injection of tolerated antigens plus adjuvant into tolerant, but not normal, mice inhibits immune responses to antigens injected concomitantly or soon thereafter. The inhibitory effect triggered by parenteral injection of tolerated proteins is known as bystander suppression or indirect effects of oral tolerance. Intraperitoneal injection of ovalbumin (OVA) plus alum adjuvant in OVA-tolerant mice soon before skin injury inhibits inflammation and improves cutaneous wound healing. However, as OVA is not a regular component of mouse chow, we tested whether indirect effects could be triggered by zein, the main protein of corn that is regularly present in mouse chow. We show that intraperitoneal injection of a single dose (10 μg) of zein plus alum adjuvant soon before skin injury in mice reduces leucocyte infiltration but increase the number of T cells and the expression of resistin-like molecule-α (a marker of alternatively activated macrophages) in the wound bed, increases the expression of transforming growth factor-β in the newly formed epidermis and reduces cutaneous scar formation. These results suggest that indirect effects of oral tolerance triggered by parenteral injection of regular dietary components may be further explored as one alternative way to promote scarless wound healing.
口服耐受是指在经肠外免疫之前，对通过口服途径接触的T细胞依赖性抗原的免疫反应性受到特异性抑制。对一种蛋白质的口服耐受不会抑制对其他不相关蛋白质的免疫反应，但将耐受抗原与佐剂经肠外注射到已产生耐受的小鼠（而非正常小鼠）体内，会抑制对同时或随后注射的抗原的免疫反应。经肠外注射耐受蛋白引发的抑制作用被称为旁观者抑制或口服耐受的间接效应。在皮肤损伤前不久，给已对卵清蛋白（OVA）产生耐受的小鼠腹腔注射OVA加明矾佐剂，可抑制炎症并促进皮肤伤口愈合。然而，由于OVA不是小鼠食物的常规成分，我们测试了玉米的主要蛋白质玉米醇溶蛋白（它在小鼠食物中经常存在）是否能引发间接效应。我们发现，在小鼠皮肤损伤前不久，腹腔注射单剂量（10μg）玉米醇溶蛋白加明矾佐剂，可减少白细胞浸润，但增加伤口床中T细胞的数量以及抗抵抗素样分子α（交替活化巨噬细胞的标志物）的表达，增加新形成表皮中转化生长因子-β的表达，并减少皮肤瘢痕形成。这些结果表明，经肠外注射常规饮食成分引发的口服耐受间接效应，作为促进无瘢痕伤口愈合的一种替代方法，可能值得进一步探索。
