Reynolds, L. A. | bioRxiv Science

bioRxiv2025

Dynamic fates of dietary antigen-specific T helper cells in a model of early life oral tolerance

Dietary antigens are first encountered in the gut during early life, when the immune system and microbiota are still maturing. In healthy individuals, oral tolerance develops towards dietary antigens: an active process which results in local and systemic immune unresponsiveness to antigens first encountered in the gut. Despite a wealth of research describing mechanisms contributing to oral tolerance in adult rodent models, questions remain about how the early life environment impacts oral tolerance development. We set out to characterize the fate(s) of CD4+ T cells during oral tolerance development using a robust early life mouse model, where controlled oral doses of dietary antigen are given directly to pups during the pre-weaning period. Orally administering 2mg of ovalbumin (OVA) daily during the third week of life was sufficient to confer oral tolerance to OVA in female and male C57BL/6 and BALB/c mice. Following early life oral OVA exposure, a large proportion of OVA-specific CD4+ T cells acquired a Th2 phenotype, alongside some OVA-specific Tregs. Following systemic challenges of OVA with an adjuvant, both OVA-specific Tregs and Th lineage-negative cells expressing anergy markers were detectable in pups given early life oral OVA, while OVA-specific Th2 cells were suppressed in comparison to pups who never received early life oral OVA. These data highlight the diverse fates of CD4+ T cells during early life oral tolerance development and maintenance, and we present a model to study oral tolerance during the early life period when dietary antigens are first encountered.

immunology↗

bioRxiv2023

The Hypolimnas misippus genome supports a common origin of the W chromosome in Lepidoptera

Moths and butterflies (Lepidoptera) have a heterogametic sex chromosome system with females carrying ZW chromosomes and males ZZ. The lack of W chromosomes in early diverging lepidopteran lineages has led to the suggestion of an ancestral Z0 system in this clade and a B chromosome origin of the W. This contrasts with the canonical model of W chromosome evolution in which the W would have originated from the same homologous autosomal pair as the Z chromosome. Despite the distinct models proposed, the rapid evolution of the W chromosome has hindered the elucidation of its origin. Here, we present high-quality, chromosome-level genome assemblies of two Hypolimnas species (Hypolimnas missipus and Hypolimnas bolina) and use the H. misippus assembly to explore the evolution of W chromosomes in butterflies and moths. We show that in H. misippus the W chromosome has higher similarity to the Z chromosome than any other chromosome, which could suggest a possible origin from the same homologous autosome pair as the Z chromosome. However, using genome assemblies of closely related species (ditrysian lineages) containing assembled W chromosomes, we present contrasting evidence suggesting that the W chromosome might have evolved from a B chromosome instead. Crucially, by using a synteny analysis to infer homology, we show that W chromosomes are likely to share a common evolutionary origin in Lepidoptera. This study highlights the difficulty of studying the evolution of W chromosomes and contributes to better understanding its evolutionary origins. SignificanceButterflies and moths have a sex determination system in which females carry two different sex chromosomes, Z and W, while males carry two copies of the Z. The evolutionary origin of the W chromosome has been elusive, with many possible scenarios being suggested, such as the independent evolution of W chromosomes in many butterfly and moth species. Here, we present genome assemblies of two Hypolimnas butterfly species and use one of them to shed light on the evolution of the W chromosome. We show that W chromosomes across butterflies and moths are very similar which suggests a shared common origin.

genomics↗