Preconceptional Immunization Can Modulate Offspring Intrathymic IL-17-Producing gamma delta T Cells with Epigenetic Implications Mediated by microRNAs

Autor(es)

de-Sousa, Thamires Rodrigues ^[1] ; Pessoa, Rodrigo ^[1] ; Nascimento, Andrezza ^[1] ; Fagundes, Beatriz Oliveira ^[1] ; Sgnotto, Fabio da Ressureicao ^[2] ; da Silva Duarte, Alberto Jose ^[3] ; Sanabani, Sabri Saeed ^[1] ; Victor, Jefferson Russo ^{[1, 4, 5]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Med Sch, Div Clin Dermatol, Lab Med Invest LIM 56, BR-05403000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Med Sch, Div Hematol, BR-01246000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Med Sch, Div Pathol, BR-05403000 Sao Paulo - Brazil

^[4] Sch Hlth Sci, Fac Metropolitanas Unidas FMU, BR-04505002 Sao Paulo - Brazil

^[5] Santo Amaro Univ UNISA, Med Sch, BR-04829300 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 12 JUN 2021.
• Citações Web of Science: 0

Resumo

The mechanisms through which maternal immunization can modulate offspring thymic maturation of lymphocytes are not fully understood. Here, we aimed to evaluate whether maternal OVA-immunization can inhibit the maturation of IL-17-producing gamma delta T cells in offspring thymus, and if this mechanism has epigenetic implications mediated by microRNAs (miRNAs) expression. Wild-type (WT) C57BL/6 females were immunized with OVA in Alum or Alum alone and were mated with normal WT males. Evaluating their offspring thymus at 3 or 20 days old (d.o.), we observed that maternal OVA immunization could inhibit the thymic frequency of offspring CD27- and IL-17(+) gamma delta T cells at the neonatal and until 20 days old. Furthermore, we evaluated the expression of function-related gamma and delta variable gamma delta TCR chains (V gamma 1, V gamma 2, V gamma 3, V delta 4, and V delta 6.3), observing that maternal OVA-immunization inhibits V gamma 2 chains expression. The small RNAs (sRNAs), particularly miRNAs, and messenger RNAs (mRNA) expression profiles by pools of thymus tissue samples (from 9 to 11 mice) from offspring OVA-immunized or Alum-immunized mothers were analyzed via Illumina sequencing platform and bioinformatics approaches. Using a fold change >4, our results showed that seven miRNAs (mmu-miR-126a-3p, 101a-3p, 744-3p,142-5p, 15a-5p, 532-5p, and 98-5p) were differentially expressed between both groups. Ten target genes were predicted to interact with the seven selected miRNAs. There were no enriched categories of gene ontology functional annotation and pathway enrichment analysis for the target genes. Interestingly, four of the identified miRNAs (mmu-miR-15a, mmu-miR-101 mmu-miR-126, and mmu-miR-142) are related to IL-17 production. Our data is of significance because we demonstrate that maternal immunization can modulate offspring thymic maturation of IL-17-producing gamma delta T cells possibly by an epigenetic mechanism mediated by miRNAs. (AU)

• Processo FAPESP: 18/05181-7 - Avaliação translacional do efeito modulador e/ou regulador dos anticorpos IgG na maturação de linfócitos TCD4, TCD8, nTreg, Tgammadelta e B intra-tímicos de neonatos.
• Beneficiário: Alberto José da Silva Duarte
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/08631-3 - Composição e diversidade da comunidade bacteriana no reservatório de Billings através do sequenciamento de nova geração do gene 16S rRNA
• Beneficiário: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Modalidade de apoio: Auxílio à Pesquisa - Regular