We are looking for motivated PhD and/or Postdocs for exciting projects related to:
1) Cancer
2) Food Allergy
How does the immune system work in these settings?

Join us and find out!

Contact me at:
arielm@tauex.tau.ac.il

This project was carried out by Dr. Naama Epstein-Rigbi with the assistance of many others. Huge thanks to our patients, the medical team at Shamir Medical Center and my group at the Tel Aviv University!
The the full preprint can be found here: biorxiv.org/cgi/content/....

Our findings suggest that CD300b and CD300f may be used as peripheral biomarkers to monitor OIT response. Moreover, this innate reprogramming may be a key piece of the puzzle in achieving long-term immune tolerance.

Interestingly, patients with atopic dermatitis or multiple food allergies had lower inhibitory CD300f at baseline, but OIT helped "reverse" this deficit by increasing CD300f expression during the maintenance phase.

These markers correlated with clinical success of OIT. In fact, we found that lower CD300b in monocytes and higher CD300f in eosinophils both correlate with a greater reduction in allergen-specific IgE.

Early in treatment, we observed a significant downregulation of the activating receptor CD300b across all myeloid cells. Simultaneously, the inhibitory receptor CD300f increased longitudinally, specifically on eosinophils.

The core finding of our research is that OIT shifts the balance of myeloid cells, including eosinophils, monocytes, and neutrophils from an "activating" state toward an "inhibitory" one by dynamically regulating CD300 receptors.

Oral Immunotherapy (OIT) induce desensitization and the majority of studies focused on its effects on T-cells. The role and phenotypes of myeloid cells during OIT is less clear. Our study reveals "reprogramming" of these innate effectors during treatment.

Sharing our new preprint summarizing our study on how oral immunotherapy shifts the immune balance of myeloid cells biorxiv.org/cgi/content/....
@FoodAllergyFund

Together, these data provide a mechanistic framework for IL-4/IL-13 targeted therapies. These tissue-specific effects may be highly relevant for biologics targeting IL-4 and/or IL-13 across EGIDs, including EoE and EoG.
👉 www.biorxiv.org/content/10.6...

Mechanistically, we uncover non-redundant receptor functions:
• IL-4Rα is required for immune cell recruitment and tissue remodeling
• IL-13Rα1 selectively controls epithelial remodeling, independent of inflammatory infiltration

RNA-seq analyses revealed coordinated transcriptional remodeling of the gastric mucosa:
⬆️ epithelial remodeling, ECM & proteases
⬇️ gastric transport, acid secretion & metabolic programs
Pointing to epithelial functional reprogramming rather than epithelial loss.

Using skin sensitization followed by intragastric oxazolone challenge, we developed a mouse model that recapitulates key features of human EoG:
• Eosinophil & mast-cell accumulation
• Epithelial thickening & foveolar elongation
• Subepithelial fibrosis

EoG is increasingly recognized and is part of Eosinophil Gastrointestinal Disorders (EGIDs). Yet its pathogenesis remains poorly defined.
In particular, how type 2 cytokines shape immune infiltration and tissue remodeling in the stomach has been unclear.

🧵 New preprint on bioRxiv!
We establish an experimental model of eosinophilic gastritis (EoG) and dissect how IL-4 and IL-13 receptor pathways differentially regulate inflammation and epithelial remodeling in the stomach.
👉 www.biorxiv.org/content/10.6...

Distinct Roles for TSLP and IL-33 in Experimental Eosinophilic Esophagitis YouTube video by Allergy

Short summary and the highlights of our findings: "Distinct Roles for TSLP and IL-33 in Experimental Eosinophilic Esophagitis" youtu.be/Hbic3xv38yY?... דרך
@YouTube

@EosinophilSoc

@AllergyEaaci

Distinct Roles for TSLP and IL-33 in Experimental Eosinophilic Esophagitis YouTube video by Allergy

Short summary and the highlights of our findings: "Distinct Roles for TSLP and IL-33 in Experimental Eosinophilic Esophagitis" youtu.be/Hbic3xv38yY?... דרך
@YouTube

@EosinophilSoc

@AllergyEaaci

The study was funded by
@usisraelbsf
@IsraelAcademy
@azrielifdn
@AstraZeneca

8/8

🧬 RNA-seq analysis of esophageal tissue revealed that TSLP controls the expression of IL-13-dependent genes central to human EoE:
🧪 Eotaxins, IL-19, FLG, KLK5, IL36RN, IL1R2
📌 TSLP shapes barrier integrity, IL-1 signaling, and epithelial differentiation.
7/8

🧪 Key finding #2
IL-33 plays a more limited role.
Il33⁻/⁻ mice showed reduced eosinophilia, but no impact on tissue remodeling suggesting non-redundant roles for TSLP and IL-33 in EoE.
6/8

🧪 Key finding #1
TSLP is essential for EoE pathogenesis.
Crlf2⁻/⁻ mice were nearly completely protected from developing EoE.
Neutralizing TSLP reduced:
✅ Eosinophilia
✅ Basal cell proliferation
✅ Vascularization
✅ Lamina propria thickening
5/8

To answer this, we used genetic and antibody-based approaches in a validated mouse model of EoE (onlinelibrary.wiley.com/doi/10.1111/...).
We studied WT, Il33⁻/⁻, and Crlf2⁻/⁻ (TSLP receptor knockout) mice, and applied neutralizing antibodies to TSLP or IL-5.
4/8

Two epithelial-derived cytokines TSLP and IL-33 have been implicated in allergic diseases.
But what is their role in EoE?
And are they redundant or functionally distinct in driving this disease?
#Immunology #EoE #Eosinophils
3/8

🔬 EoE is a chronic food allergy-induced inflammation of the esophagus that is currently on the rise. It is characterized by eosinophilia, basal cell hyperplasia, and tissue remodeling. It causes swallowing difficulties, pain, and growth delay. @EosinophilSoc #Allergy
2/8

Just published in @AllergyEaaci
Led by @dsilvaanish66 in collaboration with @RothenbergLab @ChenVarol @AstraZeneca. We reveal a non-redundant and key role for TSLP in eosinophilic esophagitis (EoE)- a chronic allergic disease of the esophagus.
onlinelibrary.wiley.com/doi/10.1111/...
🧵👇
1/8

Total disgrace!

This is unacceptable. A total disgrace. Shame on the organizers. Leave science out of it! I am appalled to see this in the microbiology community 🦠

Evolving role for eosinophils in cancer: from bench to bedside Eosinophils are increasingly recognized as important immune cells in the tumor microenvironment (TME). Recent technological advancements reveal their …

Our recent review is out!
Great working on this with
@GrisaruSharon and @BethJacobsen
www.sciencedirect.com/science/arti...

Thanks Shai

Distinct roles for thymic stromal lymphopoietin (TSLP) and IL-33 in experimental eosinophilic esophagitis Rationale: Thymic 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 a...

Preprint 📢📢
Epithelial cell-derived cytokines such as TSLP snd IL-33 likely have key roles in the initiation of allergic diseases. We show that despite co-upregulation/expression of IL-33 and TSLP in EoE, TSLP has a dominant role.

www.biorxiv.org/content/10.1...