RESUMEN
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.
Asunto(s)
Apendicitis , Inflamación , Células T Invariantes Asociadas a Mucosa , Humanos , Apendicitis/patología , Apendicitis/inmunología , Células T Invariantes Asociadas a Mucosa/inmunología , Células T Invariantes Asociadas a Mucosa/metabolismo , Inflamación/patología , Inflamación/inmunología , Inflamación/metabolismo , Citocinas/metabolismo , Enfermedad Aguda , Activación de Linfocitos/inmunología , Organoides , Movimiento Celular , Niño , Masculino , Femenino , Mucosa Intestinal/patología , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Apéndice/patología , Apéndice/inmunologíaRESUMEN
Immunoglobulin G4 (IgG4)-related disease is an autoimmune disease that forms tumorous lesions. Several cases involving various organs are reported, however, IgG4-related disease involving appendix has not been reported yet. In this report, we presented a case of IgG4-related disease of appendix, which raised a suspicion of appendiceal tumor or usual appendicitis and, therefore, led to unnecessary surgical resection. IgG4-related disease should be considered in the differential diagnosis for a mass-like swelling of the appendix, in order to avoid unnecessary surgery.