Exhaustion profile on classical monocytes after LPS stimulation in patients with Crohn’s disease

Author:

Oliveira Lucas Pires Garcia,Xavier Rafaela GomesORCID,Nora Claudia Concer Viero,Mangueira Cristóvão Luis Pitangueira,Rosseto Eliane Aparecida,Aloia Thiago,Gil Jaime Zaladek,Neto Arceu Scanavini,Lopes Filipa Blasco Tavares Pereira,Carvalho Karina InacioORCID

Abstract

AbstractCrohn’s disease is an inflammatory bowel disease that induces diarrhea, abdominal pain, weight loss, and even susceptibility to developing tumors. The immune system is pivotal in the gastrointestinal tract, promoting tolerance against commensal antigens and food. However, Crohn’s disease manifests by a breakdown in the mechanism of immune tolerance and the consequent development of exacerbated chronic inflammatory responses. The involvement of the immune system is pivotal in Crohn’s disease, with a wide range of immune cells being altered, which may include monocytes. Taking the lack of knowledge regarding monocytes in Crohn’s disease, we ought to elucidate the cytokine production and activation profile of monocyte subsets in the pathophysiology. We used multiparametric flow cytometry, quantified gene expression using qPCR, and made a correlation matrix regarding flow cytometry data and qPCR using a bioinformatic approach to examine monocyte status. The Corhn’s patients show a decrease in all subsets of monocytes.In contrast, classical monocytes show an exhaustion profile with increased expression of CD38 and decreased production of IL-1β after LPS stimulation in the patients’ group. These results indicate that monocyte subsets are differentially involved in the pathophysiology. These findings may suggest that monocytes favor disease chronicity and lack immune response resolution.

Publisher

Cold Spring Harbor Laboratory

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