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

TY - JOUR

T1 - Nmes1 is a novel regulator of mucosal response influencing intestinal healing potential

AU - Hamley, Madeleine

AU - Leyk, Stephanie

AU - Casar, Christian

AU - Liebold, Imke

AU - Jawazneh, Amirah Al

AU - Lanzloth, Clarissa

AU - Böttcher, Marius

AU - Haas, Helmut

AU - Richardt, Ulricke

AU - Rothlin, Carla V

AU - Jacobs, Thomas

AU - Huber, Samuel

AU - Adlung, Lorenz

AU - Pelczar, Penelope

AU - Henao-Mejia, Jorge

AU - Bosurgi, Lidia

N1 - © 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.

PY - 2024/2

Y1 - 2024/2

N2 - The 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.

AB - The 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.

U2 - 10.1002/eji.202350434

DO - 10.1002/eji.202350434

M3 - SCORING: Journal article

C2 - 37971166

VL - 54

SP - e2350434

JO - EUR J IMMUNOL

JF - EUR J IMMUNOL

SN - 0014-2980

IS - 2

ER -