
果蠅體液免疫反應受JAK/STAT、NF-κB和GATA信號通路的協調調控。


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The two arms of innate immunity consist of the cell-mediated cellular defenses and the systemic humoral immune responses. Drosophila humoral immune defenses in the context of antimicrobial immunity, particularly the regulation and activation of antimicrobial peptide secretion from the fat body, have been studied extensively. How Drosophila regulates humoral immunity against another major natural enemy, the parasitoid wasp, is less well-characterized. In this study, we focused on a gene crucial in anti-parasitoid immunity, lectin-24A , which is specifically induced following parasitization. We found that a fluorescent reporter driven by the region upstream of lectin-24A showed localized posterior expression in the larval fat body, the Drosophila tissue mediating humoral immunity. Furthermore, with RNA sequencing of the anterior and posterior fat body sections, we found that components of JAK/STAT, GATA, and Toll pathways were regulated differentially in the anterior-posterior axis of the fat body and/or by infection. Predicted binding motifs for transcription factors in all three of these pathways were identified in the 444bp upstream region of the lectin-24A gene, where scrambling these motifs leads to reduced basal or induced expression of the fluorescent reporter. Investigating each of these pathways, we found that JAK/STAT, the GATA factor Pannier, and the NF-κB factor dorsal all modulate the expression of lectin-24A . The binding motifs associated with these transcription factors were also enriched in the upstream sequences of parasitism-induced genes in the fat body. Taken together, these results indicate that JAK/STAT, Pannier, and NF-κB signaling are involved in the regulation of lectin-24A and, more generally, Drosophila humoral anti-parasitoid immunity after infection.

### Competing Interest Statement

The authors have declared no competing interest.

A humoral immune response to parasitoid wasps in Drosophila is regulated by JAK/STAT, NF-κB and GATA

寄生蜂感染下果蠅體液免疫反應受jak-stat-nf-κb和gata調控


寄生蜂感染下果蠅體液免疫反應受JAK/STAT、NF-κB和GATA調控


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CTLA-4是一個關鍵的T細胞抑制性分子，其缺失會導致斑馬魚出現類似人類炎症性腸病的表型，包括腸道上皮屏障完整性受損、免疫細胞浸潤、腸道微生物失衡等。這為闡明CTLA-4在炎症性腸病發病機制中的作用提供了重要證據。


Inflammatory bowel disease (IBD) is a chronic and relapsing immune-mediated disorder characterized by intestinal inflammation and epithelial injury. The underlying causes of IBD are not fully understood, but genetic factors have implicated in genome-wide association studies, including CTLA-4, an essential negative regulator of T cell activation. However, establishing a direct link between CTLA-4 and IBD has been challenging due to the early lethality of CTLA-4 knockout mice. In this study, we identified zebrafish Ctla-4 homolog and investigated its role in maintaining intestinal immune homeostasis by generating a Ctla-4-deficient ( ctla-4-/- ) zebrafish line. These mutant zebrafish exhibit reduced weight, along with impaired epithelial barrier integrity and lymphocytic infiltration in their intestines. Transcriptomics analysis revealed upregulation of inflammation-related genes, disturbing immune system homeostasis. Moreover, single-cell RNA-sequencing analysis indicated increased Th2 cells and interleukin 13 expression, along with decreased innate lymphoid cells and upregulated proinflammatory cytokines. Additionally, Ctla-4-deficient zebrafish exhibited reduced diversity and an altered composition of the intestinal microbiota. All these phenotypes closely resemble those found in mammalian IBD. Lastly, supplementation with Ctla-4-Ig successfully alleviated intestinal inflammation in these mutants. Altogether, our findings demonstrate the pivotal role of Ctla-4 in maintaining intestinal homeostasis. Additionally, they offer substantial evidence linking CTLA-4 to IBD and establish a novel zebrafish model for investigating both the pathogenesis and potential treatments.

### Competing Interest Statement

The authors have declared no competing interest.

All data generated or analyzed during this study are included in this article and its supplementary information files. The RNA-seq and scRNA-seq data for this study have been deposited in NCBI Gene Expression Omnibus (GEO) (<https://www.ncbi.nlm.nih.gov/geo/>) under accession numbers GSE255304 and GSE255303, respectively. The 16S rRNA sequencing data in this study have been deposited in the NCBI Sequence Read Archive (SRA) (<https://www.ncbi.nlm.nih.gov/sra/>) with an accession number of BioProject PRJNA1073727.

Unraveling the Role of Ctla-4 in Intestinal Immune Homeostasis: Insights from a novel Zebrafish Model of Inflammatory Bowel Disease

解開ctla-4在腸道免疫穩態中的作用-基於一種新型斑馬魚炎症性腸病模型的洞見


解開CTLA-4在腸道免疫穩態中的作用：基於一種新型斑馬魚炎症性腸病模型的洞見



γδ T細胞透過分泌IL-3調控皮膚感覺神經元對過敏原的反應閾值,從而影響過敏反應的發生。


A γδ T cell–IL-3 signalling axis is defined that controls the allergen responsiveness of cutaneous sensory neurons, leading to evidence for an immune rheostat that governs sensory neuronal responses to allergens on first exposure.

A γδ T cell–IL-3 axis controls allergic responses through sensory neurons - Nature

如何有效地利用免疫細胞調控過敏性神經元的活化閾值