Biology subjects

Munitz, A.

Publications and source records attributed to Munitz, A..

6 recordsLinked to original sources

bioRxiv2026

IL-13 Induces a Tuft Cell-Intrinsic CD45 Checkpoint to Limit Intestinal Type 2 Immunity

Tuft cells initiate intestinal type 2 immunity, yet the mechanisms that restrain excessive tuft cell activation remain poorly understood. Here, we identify the receptor tyrosine phosphatase CD45 (Ptprc), previously considered a hematopoietic marker, as a regulator of intestinal tuft cell function. CD45 expression is restricted to a subset of tuft cells and is induced by helminth infection and IL-13. Epithelial-specific deletion of Ptprc activated a tuft cell inflammatory program, promoted an epithelial inflammatory state, and increased eosinophil accumulation at homeostasis. During Heligmosomoides polygyrus bakeri infection, CD45 deficiency enhanced ILC2 and Th2 responses and reduced parasite burden, demonstrating that epithelial CD45 limits type 2 immunity in vivo. Accordingly, in intestinal organoids, CD45 was dispensable for IL-13-driven tuft cell differentiation but restrained IL-13-responsive transcriptional programs. Mechanistically, CD45-deficient tuft cells exhibited altered protein abundance of STAT5 and IL17RB, implicated in tuft cell immune regulation. Together, these findings identify CD45 as a tuft cell-intrinsic regulatory checkpoint that restrains intestinal type 2 immunity through an IL-13-induced negative-feedback circuit.

immunology↗

bioRxiv2026

Dynamic Regulation of CD300b, and CD300f on Myeloid Cells in Oral Immunotherapy

IntroductionOral immunotherapy (OIT) induces desensitization in IgE-mediated food allergy, yet the role of myeloid cells in acquisition of tolerance is unclear. CD300 receptors regulate activation of myeloid cells, with CD300f acting as an inhibitory receptor and CD300b as an activating receptor. Their modulation during OIT may reflect effector cell reprogramming and serve as biomarkers of treatment response. MethodsThirty-five patients undergoing OIT were prospectively enrolled. Peripheral blood was collected at baseline and first 3 months of up-dosing; 19 patients completed sampling upon reaching maintenance. CD300b and CD300f expression in eosinophils, monocytes, and neutrophils was analyzed by flow cytometry. Allergen-specific IgE and IgG4 were measured by ImmunoCAP. Associations with clinical parameters were assessed using logistic regression. Results. Baseline CD300b was higher in patients with lower starting doses (p[≤]0.05). CD300f expression was lower in those with atopic dermatitis or multiple food allergies (p[≤]0.03). A significant downregulation of CD300b expression in the surface of eosinophils, monocytes, and neutrophils, was noted early in treatment (p[≤]0.05). Expression of CD300f was slightly but non-significantly increased. Longitudinally, the expression of CD300f increased on eosinophils, whereas CD300b expression decreased on the surface of monocytes and neutrophils. Specific IgE reduction correlated with downregulation of CD300b expression in monocytes (R=0.51, p=0.02) and higher CD300f expression in eosinophils (R=-0.45, p=0.05). ConclusionsDownregulation of CD300b and upregulation of CD300f during OIT suggests myeloid cell reprogramming toward a less inflammatory phenotype. These dynamic changes in expression and their correlation with serologic markers of desensitization, suggest CD300b and CD300f as candidate biomarkers for understanding and monitoring OIT response. Key MessageO_LIOIT is associated with downregulation of the activating receptor CD300b and upregulation of the inhibitory receptor CD300f on myeloid cells. C_LIO_LIMyeloid cell reprogramming accompanies OIT, extending immune tolerance beyond adaptive regulatory mechanisms. C_LIO_LICD300b and CD300f expression dynamics correlate with clinical dosing and serologic markers of OIT response. C_LI

immunology↗

bioRxiv2026

Differential roles for IL-4Rα and IL-13Rα1in immune cell infiltration and epithelial remodeling in experimental eosinophilic gastritis

RationaleEosinophilic gastritis (EoG) is a chronic inflammatory disease characterized by infiltration of eosinophils and mast cells, epithelial remodeling, and fibrosis. Although EoG is increasingly recognized as a distinct type 2 inflammatory disease, the cellular and molecular events that drive disease pathogenesis remain poorly understood. This is due in part to the absence of robust and physiologically relevant experimental models that recapitulate human disease. MethodsExperimental EoG was induced in wild type and Il13ra1-/-mice by repeated intragastric oxazolone challenges in skin-sensitized mice. IL-4R1 was neutralized using antibodies. Gastric histopathology was determined by H&E, anti-Ki67, chloroacetate esterase and anti-MBP staining. Gastric RNA was subjected to RNA sequencing. ResultsExperimental EoG resulted in robust gastric eosinophilia, mastocytosis, epithelial remodeling, and subepithelial fibrosis. Transcriptomic profiling of gastric tissue revealed broad upregulation of type 2 cytokine and epithelial-remodeling genes, including Il4ra, Il4i1, Ccl5, Muc4, Mmp10, Mcpt1/2, Areg, Pparg and Tff2. The transcriptome profile of experimental EoG was markedly distinct from that of experimental EoE despite both models being initiated by oxazolone, suggesting that identical inflammatory triggers elicit tissue-specific and context-dependent transcriptional programs. Blockade of IL-4R signaling abrogated both eosinophil and mast cell infiltration and attenuated epithelial remodeling, whereas genetic deletion of Il13ra1 selectively suppressed epithelial remodeling without affecting inflammatory cell recruitment. ConclusionThese findings establish experimental EoG as a robust model for dissecting the cellular and molecular mechanisms driving gastric type 2 inflammation. They further define receptor-specific roles for IL-4R and IL-13R1 in coordinating immune infiltration and epithelial remodeling in EoG.

immunology↗

bioRxiv2025

Distinct roles for thymic stromal lymphopoietin (TSLP) and IL-33 in experimental eosinophilic esophagitis

RationaleThymic stromal lymphopoietin (TSLP) and IL-33 are alarmins implicated in EoE pathogenesis by activating multiple cells including mast cells (MCs). Whether TSLP or IL-33 have a role in EoE and whether their activities are distinct requires further investigation. MethodsExperimental EoE was induced in wild type (WT) Il33-/-and Crlf2-/- mice. TSLP or IL-5 were neutralized using antibodies. Esophageal histopathology was determined by H&E, anti-Ki67, anti-CD31 and anti-MBP staining. Esophageal RNA was subjected to RNA sequencing. Bone marrow-derived MCs were activated with TSLP and IL-13 was determined (ELISA) ResultsTSLP and IL-33 were overexpressed in human and experimental EoE. Human and mouse esophageal MCs displayed the highest level of Crlf2 (TSLPR) compared to other immune cells. Crlf2-/- mice were nearly-completely protected from EoE, and TSLP neutralization resulted in decreased basal cell proliferation, eosinophilia, lamina propria thickening and vascularization. Induction of experimental EoE in Il33-/- mice resulted in reduced eosinophilia but no alterations in tissue remodeling were observed compared to WT mice. RNA sequencing revealed that TSLP regulates the expression of key genes associated with human EoE (e.g. eotaxins, Il19, Klk5, Flg, Il36rn, Il1r2) and suggest a role for TSLP in regulating IL-1 signaling, barrier integrity and epithelial cell differentiation. Experimental EoE was characterized by a MC-associated gene signature and elevated MCs. Activation of MCs with TSLP resulted in secretion of IL-13. ConclusionTSLP and IL-33 have non-redundant functions in experimental EoE. This study highlights TSLP as an upstream regulator of IL-13 and a potential therapeutic target for EoE.

immunology↗

bioRxiv2023

Engineering mice for female-biased progeny without impacting genetic integrity and litter size

The ability to influence the sex ratio of mammalian offspring has applications in agriculture and animal welfare. Here we describe a genetic system in mice that produces predominantly female progeny, reaching approximately ninety percent, without affecting litter size or introducing genetic modifications into the offspring. The system consists of a doxycycline-regulated cassette inserted into the Y chromosome, encoding dCas9 and RNA guides intended to impair the function of Y bearing sperm. While the cassette was originally intended to repress a spermatid maturation gene, our analyses did not detect meaningful changes in gene expression or sperm function that would account for the phenotype. Nevertheless, male mice carrying the cassette consistently produced female biased litters, and the effect was reversed by doxycycline, confirming that it depends on cassette expression. Similar female bias was observed following in vitro fertilization using sperm from transgenic males. These findings demonstrate a reproducible, genetically confined, and conditionally regulated system for sex ratio bias in mice. The strategy may prove adaptable across species, even without a complete mechanistic understanding. Graphical AbstractA single line genetic system producing female biased, genetically unmodified progeny in mice by conditionally impairing Y bearing sperm. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/568055v4_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@5f23b3org.highwire.dtl.DTLVardef@20ed2corg.highwire.dtl.DTLVardef@1b3007dorg.highwire.dtl.DTLVardef@e54cf6_HPS_FORMAT_FIGEXP M_FIG C_FIG One sentence summaryY chromosome manipulation yields mostly female mice, preserving litter size without genetic alteration in females. Significance statementThis study describes a genetic approach for producing predominantly female offspring in mice without altering litter size or transmitting genetic modifications to the progeny. A cassette inserted into the Y chromosome of males induces a strong female bias in offspring through a mechanism that remains unclear. The female offspring do not inherit the transgene and are genetically unmodified. This system provides a simple and conditional platform for sex ratio control in mammals, with potential applications in animal breeding and welfare.

bioengineering↗

bioRxiv2019

A genetic system for generating single-sex progeny in mice

The ability to preselect the sex of livestock is economically beneficial and significantly increases the welfare and proper use of animals. In the poultry industry, for example, almost all males are brutally and unnecessarily killed shortly after hatching. The labor and associated costs of separation of females from males, as well as the massive killing of males, could be reduced by using a system that biases the sex of the progeny. Here, we provide a first proof of concept for such a system by crossing two genetically engineered mouse lines. The maternal line encodes a functional Cas9 protein on an autosomal chromosome, whereas the paternal line encodes guide RNAs on the Y chromosome targeting vital mouse genes. After fertilization, the presence of both the Y-encoded guide RNAs from the paternal sperm and the Cas9 protein from the maternal egg target the vital genes in males. We show that this breeding consequently self-destructs solely the males. Our results pave the way for a biased sex production of livestock, thus saving labor, costs, and eliminating substantial animal suffering.

developmental biology↗