Ustekinumab Inhibits T Follicular Helper Cell Differentiation in Patients With Crohn's Disease.

Cellular and Molecular Gastroenterology and Hepatology
Anna-Maria GlobigPeter Hasselblatt

Abstract

The pathogenesis of chronic inflammatory bowel diseases (Crohn's disease [CD] and ulcerative colitis) involves dysregulated TH1 and TH17 cell responses, which can be targeted therapeutically by the monoclonal antibody Ustekinumab directed against the joint p40 subunit of IL-12 and IL-23. These cytokines may also regulate the differentiation of T follicular helper (TFH) cells, which promote B cell function in germinal centers. However, the role of TFH cells in CD pathogenesis and impact of Ustekinumab therapy on TFH cell fate in patients are poorly defined. Lymphocytes were isolated from peripheral blood (n=45) and intestinal biopsies (n=15) of CD patients or healthy controls (n=21) and analyzed by flow cytometry to assess TFH cell phenotypes and functions ex vivo. In addition, TFH cell differentiation was analyzed in the presence of Ustekinumab in vitro. TFH cell frequencies in the intestine as well as peripheral blood were associated with endoscopic as well as biochemical evidence of CD activity. CD patients with clinical response to Ustekinumab, but not those with response to anti-TNF antibodies, displayed reduced frequencies of circulating TFH cells in a concentration-dependent manner while the TFH phenotype was not affected...Continue Reading

Citations

Sep 1, 2021·Journal of Translational Medicine·Pauline BeurierArsène Mekinian
Sep 3, 2021·Gastroenterology Research and Practice·Lulu SunDashan Wang

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Methods Mentioned

BETA
biopsies
flow cytometry
biopsy
PMA
Flow Cytometric
ELISA

Software Mentioned

Prism
FlowJo
GraphPad

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