Biology subjects

Schraml, B.

Publications and source records attributed to Schraml, B..

3 recordsLinked to original sources

bioRxiv2025

Il33 expressing cDC2s promote expansion of ILC2s and eosinophilia in fungal airway inflammation in male mice

Eosinophilic allergic asthma is often associated with fungal sensitization and represents the dominant form of asthma in adolescents. The mechanisms by which lung eosinophilia is regulated in this context are incompletely understood. Here, we demonstrate that type 2 innate lymphoid cells (ILC2s) are generally required in addition to Th2 cells for Aspergillus fumigatus-elicited eosinophilic lung inflammation in mice and this effect was independent of ILC2-derived IL-5. Surprisingly, expansion of ILC2s in male mice was ST2-independent, but required expression of Il33 in cDC2s induced by Th2-derived IL-4/13. This IL-33-plus IL-4-regulated transcriptional module in cDC2s included expression of factors associated with activation of ILC2s and was restricted to CCR7+ cDC2s in the inflamed lung. Our findings uncovered a novel intimate cross-talk between IL-33+ cDC2s, ILC2s and Th2 cells to orchestrate eosinophilia in a sex-dependent manner upon A. fumigatus-induced allergic lung inflammation.

immunology↗

bioRxiv2024

Susceptibility to inflammatory bowel diseases promotes invasive carcinomas in a murine model of ATF6-driven colon cancer

Chronic inflammation in inflammatory bowel disease (IBD) patients represents a risk factor for developing colitis-associated cancer (CAC). We previously linked the endoplasmic reticulum unfolded protein response (UPRER) signal transducer activating transcription factor 6 (ATF6) with spontaneous microbiota-dependent colonic adenoma development in mice expressing epithelial-specific activated ATF6 (nATF6IEC). To investigate IBD-related risk factors in ATF6-mediated tumorigenesis, we crossed tumor-free monoallelic (tg/wt) nATF6IEC mice with Interleukin-10 deficient mice (Il10-/-). IL10 deficiency initiated tumor susceptibility, with 77% of 12-week tg/wt;Il10-/- mice developing colonic adenomas and invasive carcinomas in this novel CAC mouse model. Tumor formation correlated with mucosal immune cell infiltration, characterized by CD11b+ granulocytes and monocytes, and mucosa-associated dysbiosis. Colonization of germ-free nATF6IEC;Il10-/- mice with minimal biosynthetic consortia and IBD stool re-established CAC, confirming microbiota-dependent ATF6-driven tumorigenesis. Increased ATF6 expression in IBD patients during active disease highlights its human relevance. Our findings show that IBD susceptibility heightens the risk for ATF6-driven tumorigenesis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/624835v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@17e280eorg.highwire.dtl.DTLVardef@177ceacorg.highwire.dtl.DTLVardef@a1916borg.highwire.dtl.DTLVardef@152374f_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2022

Loss of Bcl6 transcriptionally alters classical dendritic cells and diminishes T follicular helper cell-inducing cDC2 in mouse spleen

Conventional dendritic cells (cDC) play key roles in immune induction, but what drives their heterogeneity and functional specialization is still ill-defined. Here we show that cDC-specific deletion of the transcriptional repressor Bcl6 in mice alters the phenotype and transcriptome of cDC1s and cDC2s, while their lineage identity is preserved. Bcl6-deficient cDC1s are diminished in the periphery but maintain their ability to cross-present antigen to CD8+ T cells, confirming general maintenance of this subset. Surprisingly, the absence of Bcl6 in cDCs causes a complete loss of Notch2-dependent cDC2s in the spleen and intestinal lamina propria. DC-targeted Bcl6-deficient mice induced fewer T follicular helper cells despite a profound impact on T follicular regulatory cells in response to immunization and mounted diminished Th17 immunity to Citrobacter rodentium in the colon. Our findings establish Bcl6 as an essential transcription factor for subsets of cDC and add to our understanding of the transcriptional landscape underlying cDC heterogeneity.

immunology↗