Participação dos linfócitos no processo de reparo de feridas cutâneas de camundongos submetidos a injeção parenteral de proteínas imunologicamente toleradas

Abstract

Skin integrity is very important for health but injuries, whether accidental or from scheduled surgery, occur frequently. The repair of these injuries involves several cell types that interact in ways that is still not well understood. The failure to close the wounds within the expected time or the occurrence of pathological scars are important problems for public health, whose solution requires more effective forms of intervention and a better understanding of the mechanisms involved. The inflammatory phase of repair is important for wound closure, but exacerbated and prolonged inflammation is related with hypertrophic scars and chronic wounds. Oral tolerance is a phenomenon that promotes systemic modifications of immunological activity after antigenic contact through the oral mucosa and inhibits immune responses when antigens are subsequently injected. Oral tolerance is lymphocyte dependent and can be adoptively transferred to syngeneic animals via lymphocytes obtained from the spleen or lymph nodes. In previous studies, we have shown that a parenteral injection of previously ingested proteins, concomitantly with skin lesions, reduces the inflammatory infiltrate and improves healing. Zein is a corn protein present in mouse feed and an injection of zein plus adjuvant up to 5 days before skin wounds reduces the inflammatory infiltrate, increases the number of T lymphocytes in the wound bed, and improves healing. Data from the literature show that lymphocytes participate in the repair of skin injuries. As there are different types of lymphocytes, either resident in the skin or that migrate to the wound bed during repair, more studies are needed to verify how these cells act in wound repair. Our objective was to verify whether zein injection's positive effects depend on lymphocyte migration to the lesion area (CEUA/UFMG protocol 253/2021). We used mice that feed on food containing corn and are deficient in lymphocytes (RAG KO). or received an injection of a drug (FTY720) that inhibits the migration of peripheral lymphocytes to inflamed sites. Our results show that the absence of lymphocytes promoted a more inflammatory environment, with changes in the migration of inflammatory cells and a delay in wound closure at 7 days after injury. At 40 days after the injury, we observed that the injection of FTY720 modified the formation of the neodermis with collagen deposition without forming fiber bundles. Zein injection did not reduce inflammation and improve healing in RAG KO animals or animals receiving FTY720. The adoptive transfer of spleen cells from WT to RAG KO animals immunized with the tolerated protein promoted a positive effect of s.c injection of zein in the repair of skin lesions. These results indicate that lymphocytes are important cells for the wound repair process and also for the immunomodulatory effects of oral tolerance.