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MAIT cell activation and recruitment in inflammation and tissue damage in acute appendicitis
Yichao Zheng1,2, Fei Han1, Zhengyu Wu1
1Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
Abstract:
Mucosal-associated invariant T (MAIT) cells are antimicrobial T cells abundant in the gut, but mechanisms for their migration into tissues during inflammation are poorly understood. Here, we used acute pediatric appendicitis (APA), a model of acute intestinal inflammation, to examine these migration mechanisms. MAIT cells were lower in numbers in circulation of patients with APA but were enriched in the inflamed appendix with increased production of proinflammatory cytokines. Using the patient-derived appendix organoid (PDAO) model, we found that circulating MAIT cells treated with inflammatory cytokines elevated in APA up-regulated chemokine receptors, including CCR1, CCR3, and CCR4. They exhibited enhanced infiltration of Escherichia coli-pulsed PDAO in a CCR1-, CCR2-, and CCR4-dependent manner. Close interactions of MAIT cells with infected organoids led to the PDAO structural destruction and death. These findings reveal a previously unidentified mechanism of MAIT cell tissue homing, their participation in tissue damage in APA, and their intricate relationship with mucosal tissues during acute intestinal inflammation in humans.
Insights
Mucosal-associated invariant T (MAIT) cells migrate to inflamed appendix tissue during appendicitis. These immune cells contribute to tissue damage, revealing new insights into gut inflammation mechanisms.
Area of Science:
- Immunology
- Gastroenterology
- Microbiology
Background:
- Mucosal-associated invariant T (MAIT) cells are crucial for gut immunity but their migration during inflammation is unclear.
- Acute pediatric appendicitis (APA) offers a model to study immune cell behavior in intestinal inflammation.
Purpose of the Study:
- To investigate MAIT cell migration mechanisms into inflamed appendix tissue.
- To understand MAIT cell interactions with the gut mucosa during acute inflammation.
Main Methods:
- Analysis of MAIT cell numbers and cytokine production in APA patients.
- Utilizing patient-derived appendix organoids (PDAO) to model inflammation.
- Investigating MAIT cell infiltration in response to *Escherichia coli* in PDAO.
Main Results:
- MAIT cells were reduced in circulation but enriched in inflamed appendix tissue in APA patients.
- Inflammatory cytokines induced MAIT cell chemokine receptor expression (CCR1, CCR3, CCR4).
- MAIT cells infiltrated *E. coli*-pulsed PDAO dependent on CCR1, CCR2, and CCR4, causing tissue destruction.
Conclusions:
- A novel mechanism for MAIT cell tissue homing during intestinal inflammation was identified.
- MAIT cells actively participate in tissue damage in acute pediatric appendicitis.
- MAIT cells have a complex role in the host-pathogen interaction within mucosal tissues.
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