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Enhanced Th17 responses in the appendix of children with complex compared to simple appendicitis are associated with
Sarah-May M L The1,2,3, Renée R C E Schreurs3,4, Agata Drewniak3
1Department of Paediatric Surgery, Emma Children's Hospital, Amsterdam University Medical Center (UMC), University of Amsterdam & Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Insights
Complex appendicitis in children involves disrupted T cell responses and increased IL-17A production, linked to appendiceal microbiota changes. Further research is needed to understand this complex interplay.
Area of Science:
- Pediatric Surgery
- Immunology
- Microbiology
Background:
- Appendicitis is a common cause of acute abdominal surgery in children.
- The heterogeneity of appendicitis, ranging from simple to complex, is not well understood.
- T cell dysregulation is implicated in intestinal inflammation, but its role in pediatric appendicitis is unclear.
Purpose of the Study:
- To characterize appendiceal T cells in simple versus complex appendicitis.
- To correlate T cell immunophenotypes with appendiceal microbiota in pediatric appendicitis.
Main Methods:
- In-depth immunophenotyping of T cells from appendix samples using flow cytometry.
- Analysis of appendiceal microbiota from the same patient samples.
- Comparison of T cell phenotypes and microbiota in children with simple and complex appendicitis.
Main Results:
- Complex appendicitis showed increased T cell differentiation (loss of CD27/CD28) and decreased tissue-resident memory T cells (CD69+).
- Elevated IL-17A production by CD4+ T cells was observed in complex appendicitis.
- Increased IL-17A+ CD4+ T cells correlated with appendiceal microbiota dysregulation in complex cases.
Conclusions:
- Complex appendicitis in children is associated with disrupted local T cell responses and enhanced pro-inflammatory Th17 responses.
- These immune alterations correlate with changes in the appendiceal microbiota.
- Further investigation is required to elucidate the role of microbiota and Th17 cells in complex appendicitis development.
Introduction:
Appendicitis is one of the most common causes of acute abdominal surgery in children. The clinical course of appendicitis ranges from simple to complex appendicitis. The mechanisms underlying the heterogeneity of appendicitis in children remain largely unclear. Dysregulated T cell responses play an important role in several inflammatory diseases of the intestine, but the extend of T cell dysregulation in appendicitis in children is less well known.
Methods:
To characterize appendiceal T cells in simple and complex appendicitis we performed in-depth immunophenotyping of appendiceal-derived T cells by flow cytometry and correlated this to appendiceal-derived microbiota analyses of the same patient.
Results:
Appendix samples of twenty children with appendicitis (n = 8 simple, n = 12 complex) were collected. T cells in complex appendicitis displayed an increased differentiated phenotype compared to simple appendicitis, including a loss of both CD27 and CD28 by CD4+ T cells and to a lesser extent by CD8+ T cells. Frequencies of phenotypic tissue-resident memory CD69+CD4+ T cells and CD69+CD8+ T cells were decreased in children with complex compared to simple appendicitis, indicating disruption of local tissue-resident immune responses. In line with the increased differentiated phenotype, cytokine production of in particular IL-17A by CD4+ T cells was increased in children with complex compared to simple appendicitis. Furthermore, frequencies of IL-17A+ CD4+ T cells correlated with a dysregulation of the appendiceal microbiota in children with complex appendicitis.
Conclusion:
In conclusion, disruption of local T cell responses, and enhanced pro-inflammatory Th17 responses correlating to changes in the appendiceal microbiota were observed in children with complex compared to simple appendicitis. Further studies are needed to decipher the role of a dysregulated network of microbiota and Th17 cells in the development of complex appendicitis in children.
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