Nmes1 is a novel regulator of mucosal response influencing intestinal healing potential

Author:

Hamley Madeleine12,Leyk Stephanie12,Casar Christian13ORCID,Liebold Imke12,Jawazneh Amirah Al12ORCID,Lanzloth Clarissa12,Böttcher Marius1,Haas Helmut4,Richardt Ulricke2,Rothlin Carla V.56,Jacobs Thomas2,Huber Samuel17,Adlung Lorenz178,Pelczar Penelope1,Henao‐Mejia Jorge9,Bosurgi Lidia127ORCID

Affiliation:

1. I. Department of Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany

2. Protozoa Immunology Bernhard Nocht Institute for Tropical Medicine Hamburg Germany

3. Bioinformatics Core University Medical Centre Hamburg‐Eppendorf Hamburg Germany

4. helminGuard Sülfeld/Borstel Germany

5. Department of Immunobiology Yale University School of Medicine New Haven Connecticut USA

6. Department of Pharmacology Yale University School of Medicine New Haven Connecticut USA

7. Hamburg Center for Translational Immunology (HCTI) University Medical Center Hamburg‐Eppendorf Hamburg Germany

8. Center for Biomedical AI University Medical Center Hamburg‐Eppendorf Hamburg Germany

9. The Institute for Immunology, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA

Abstract

AbstractThe initiation of tissue remodeling following damage is a critical step in preventing the development of immune‐mediated diseases. Several factors contribute to mucosal healing, leading to innovative therapeutic approaches for managing intestinal disorders. However, uncovering alternative targets and gaining mechanistic insights are imperative to enhance therapy efficacy and broaden its applicability across different intestinal diseases.Here we demonstrate that Nmes1, encoding for Normal Mucosa of Esophagus‐Specific gene 1, also known as Aa467197, is a novel regulator of mucosal healing. Nmes1 influences the macrophage response to the tissue remodeling cytokine IL‐4 in vitro. In addition, using two murine models of intestinal damage, each characterized by a type 2‐dominated environment with contrasting functions, the ablation of Nmes1 results in decreased intestinal regeneration during the recovery phase of colitis, while enhancing parasitic egg clearance and reducing fibrosis during the advanced stages of Schistosoma mansoni infection. These outcomes are associated with alterations in CX3CR1+ macrophages, cells known for their wound‐healing potential in the inflamed colon, hence promising candidates for cell therapies.All in all, our data indicate Nmes1 as a novel contributor to mucosal healing, setting the basis for further investigation into its potential as a new target for the treatment of colon‐associated inflammation.

Funder

Werner Otto Stiftung

Publisher

Wiley

Subject

Immunology,Immunology and Allergy

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