RESUMO
AIM: The aim of this study was to clarify whether there are more regulatory T (Treg) and regulatory B (Breg) cells, and higher levels of IL-10-related transcription factors in subcutaneous immunotherapy (SCIT)-treated pollinosis patients than in non-SCIT-treated patients. METHODS: Japanese cedar pollinosis patients undergoing SCIT had received treatment for at least 2.8 years. Peripheral blood mononuclear cells were used for flow cytometer analyses and mRNA measurement. RESULTS: The numbers of type 1 regulatory T (Tr1)-like cells and Breg cells, and expression of E4BP4 mRNA by peripheral blood mononuclear cells in SCIT-treated patients were higher than those in non-SCIT-treated patients. CONCLUSION: Tr1-like cells, Breg cells and E4BP4 may be involved in the effectiveness of SCIT.
Assuntos
Linfócitos B Reguladores/imunologia , Dessensibilização Imunológica/métodos , Rinite Alérgica Sazonal/terapia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alérgenos/imunologia , Antígenos de Plantas/imunologia , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Biomarcadores/metabolismo , Circulação Sanguínea , Cryptomeria/imunologia , Feminino , Humanos , Injeções Subcutâneas , Interleucina-10/genética , Interleucina-10/metabolismo , Masculino , Pessoa de Meia-Idade , Pólen/imunologia , Rinite Alérgica Sazonal/imunologia , Adulto JovemRESUMO
Although interleukin (IL)-33 is a candidate for the aggravation of asthma, the mechanisms underlying antigen-specific IL-33 production in the lung are unclear. Therefore, we analysed the mechanisms in mice. Intra-tracheal administration of ovalbumin (OVA) evoked increases in IL-33 and IL-33 mRNA in the lungs of both non-sensitized and OVA-sensitized mice, and the increases in the sensitized mice were significantly higher than in the non-sensitized mice. However, intra-tracheal administration of bovine serum albumin did not increase the IL-33 level in the OVA-sensitized mice. Depletion of neither mast cells/basophils nor CD4+ cells abolished the OVA-induced IL-33 production in sensitized mice, suggesting that the antigen recognition leading to the IL-33 production was not related with either antigen-specific IgE-bearing mast cells/basophils or memory CD4+ Th2 cells. When a fluorogenic substrate-labelled OVA (DQ-OVA) was intra-tracheally administered, the lung cells of sensitized mice incorporated more DQ-OVA than those of non-sensitized mice. The lung cells incorporating DQ-OVA included B-cells and alveolar macrophages. The allergic IL-33 production was significantly reduced by treatment with anti-FcγRII/III mAb. Depletion of alveolar macrophages by clodronate liposomes significantly suppressed the allergic IL-33 production, whereas depletion of B-cells by anti-CD20 mAb did not. These results suggest that the administered OVA in the lung bound antigen-specific IgG Ab, and then alveolar macrophages incorporated the immune complex through FcγRII/III on the cell surface, resulting in IL-33 production in sensitized mice. The mechanisms underlying the antigen-specific IL-33 production may aid in development of new pharmacotherapies.
