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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 12 JUN 2021.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 18/05181-7 - Translational evaluation of IgG effect upon the maturation of offspring thymus derived TCD4, TCD8, nTreg, gammadeltaT and e B cells.
• Grantee: Alberto José da Silva Duarte
• Support type: Regular Research Grants
• FAPESP's process: 18/08631-3 - Bacterial Community Composition and Diversity in Billing Reservoir Examined by Massive Paralelel Sequence Analysis of 16S rRNA Genes
• Grantee: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Support type: Regular Research Grants