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Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
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Updated: May 12, 2025

Isolation of Group 2 Innate Lymphoid Cells from Mouse Nasal Mucosa to Detect the Expression of CD226
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RAG suppresses group 2 innate lymphoid cells.

Aaron M Ver Heul1, Madison Mack2, Lydia Zamidar3,4,5,6

  • 1Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, United States.

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|May 6, 2025
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Summary

Recombinase Activating Gene (RAG) suppresses group 2 innate lymphoid cells (ILC2s), key players in type 2 immunity. RAG deficiency leads to expanded ILC2s and heightened inflammation, revealing RAG

Keywords:
RAGallergicatopicdermatitisimmunologyinflammationinnate lymphoid cellmouse

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Area of Science:

  • Immunology
  • Innate Immunity
  • Adaptive Immunity

Background:

  • Adaptive immunity relies on T and B cell receptors assembled via V(D)J recombination, mediated by Recombinase Activating Gene (RAG) endonucleases.
  • Group 2 innate lymphoid cells (ILC2s) contribute to type 2 immune responses, similar to T helper 2 (Th2) cells.
  • The role of RAG in innate immune cells, particularly ILC2s, remains largely unexplored, despite RAG's known impact on natural killer (NK) cells.

Purpose of the Study:

  • To investigate the effect of Recombinase Activating Gene (RAG) on group 2 innate lymphoid cells (ILC2s).
  • To determine if RAG influences ILC2 function in a cell-intrinsic manner.
  • To identify transcriptional and epigenomic programs regulated by RAG in ILC2s.

Main Methods:

  • Analysis of ILC2 populations and cytokine production in RAG-deficient mice.
  • Assessment of RAG's impact on ILC2s independent of adaptive lymphocytes.
  • Multiomic single-cell analyses of RAG1 lineage-traced cells.

Main Results:

  • RAG-deficient mice exhibit expanded ILC2 populations with increased Interleukin-5 (IL-5) and Interleukin-13 (IL-13) production.
  • RAG deficiency exacerbates atopic dermatitis (AD)-like disease due to enhanced ILC2 activity.
  • RAG modulates ILC2 function intrinsically, suppressing key transcriptional and epigenomic programs.

Conclusions:

  • Recombinase Activating Gene (RAG) plays a novel suppressive role in innate type 2 immunity.
  • RAG directly impacts ILC2 function, independent of adaptive immunity.
  • RAG's suppression of ILC2s offers new insights into immune regulation and inflammatory diseases.