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Local Inflammatory Cues Regulate Differentiation and Persistence of CD8+ Tissue-Resident Memory T Cells
Tessa Bergsbaken1, Michael J Bevan1, Pamela J Fink1
1Department of Immunology, University of Washington, Seattle, WA 98109, USA.
Cell Reports
|April 6, 2017
Summary
Intestinal inflammation promotes the development of tissue-resident memory T (Trm) cells, crucial for immunity. Cytokines like interferon-beta and interleukin-12, produced by macrophages, regulate Trm cell abundance and persistence.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Pathogens often infect at mucosal surfaces, where tissue-resident memory T (Trm) cells are vital for protection.
- The specific signals guiding Trm cell differentiation in different tissues are not well understood.
Purpose of the Study:
- To investigate the role of intestinal inflammation and associated cytokines in regulating CD8+ Trm cell differentiation and persistence during Yersinia infection.
Main Methods:
- Studied CD8+ T cell recruitment and Trm differentiation in the context of Yersinia infection.
- Analyzed the impact of interferon-beta (IFN-β) and interleukin-12 (IL-12) on Trm markers like CD103.
- Utilized knockout mouse models (Type I interferon-receptor or IL-12-receptor deficient) and assessed Trm cell populations.
- Investigated the source of IFN-β and IL-12 by examining intestinal macrophages and CCR2+ cells.
Main Results:
- CD8+ T cell recruitment to inflamed intestinal sites was essential for differentiating the CD103-CD69+ Trm subset.
- Elevated IFN-β and IL-12 in the intestinal microenvironment influenced Trm markers, including CD103.
- T cells lacking Type I interferon or IL-12 receptor signaling showed defective CD103-CD69+ Trm differentiation and reduced persistence.
- Intestinal macrophages were identified as primary producers of IFN-β and IL-12 during infection.
- Depletion of CCR2+ IL-12-producing cells diminished the CD103- Trm population.
Conclusions:
- Intestinal inflammation actively shapes the diversity and quantity of Trm cells.
- IFN-β and IL-12 signaling are critical for optimal intestinal Trm cell differentiation and long-term immunity.
- Macrophages play a key role in orchestrating Trm cell responses within the gut mucosa.
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