Global amphibian declines are compounded by deadly disease outbreaks caused by the chytrid fungus, Batrachochytrium dendrobatidis (Bd). Much has been learned about the roles of amphibian skin-produced antimicrobial components and microbiomes in controlling Bd, yet almost nothing is known about the roles of skin-resident immune cells in anti-Bd defenses. Mammalian mast cells reside within and serve as key immune sentinels in barrier tissues like skin. Accordingly, we investigated the roles of Xenopus laevis frog mast cells during Bd infections. Our findings indicate that enrichment of X. laevis skin mast cells confers anti-Bd protection and ameliorates the inflammation-associated skin damage caused by Bd infection. This includes a significant reduction in infiltration of Bd-infected skin by neutrophils, promoting mucin content within cutaneous mucus glands, and preventing Bd-mediated changes to skin microbiomes. Mammalian mast cells are known for their production of the pleiotropic interleukin-4 (IL4) cytokine and our findings suggest that the X. laevis IL4 plays a key role in manifesting the effects seen following cutaneous mast cell enrichment. Together, this work underscores the importance of amphibian skin-resident immune cells in anti-Bd defenses and illuminates a novel avenue for investigating amphibian host–chytrid pathogen interactions.

The evolutionary conservation of non-core RAG regions suggests significant roles that might involve quantitative or qualitative alterations in RAG activity. Off-target V(D)J recombination contributes to lymphomagenesis and is exacerbated by RAG2’ C-terminus absence in Tp53^−/− mice thymic lymphomas. However, the genomic stability effects of non-core regions from both Rag1^c/c and Rag2^c/c in BCR-ABL1⁺ B-lymphoblastic leukemia (BCR-ABL1⁺ B-ALL), the characteristics, and mechanisms of non-core regions in suppressing off-target V(D)J recombination remain unclear. Here, we established three mouse models of BCR-ABL1⁺ B-ALL in mice expressing full-length RAG (Rag^f/f), core RAG1 (Rag1^c/c), and core RAG2 (Rag2^c/c). The Rag^c/c (Rag1^c/c and Rag2^c/c) leukemia cells exhibited greater malignant tumor characteristics compared to Rag^f/f cells. Additionally, Rag^c/c cells showed higher frequency of off-target V(D)J recombination and oncogenic mutations than Rag^f/f. We also revealed decreased RAG cleavage accuracy in Rag^c/c cells and a smaller recombinant size in Rag1^c/c cells, which could potentially exacerbate off-target V(D)J recombination in Rag^c/c cells. In conclusion, these findings indicate that the non-core RAG regions, particularly the non-core region of RAG1, play a significant role in preserving V(D)J recombination precision and genomic stability in BCR-ABL1⁺ B-ALL.