Case Report: IL-21 and Bcl-6 Regulate the Proliferation and Secretion of Tfh and Tfr Cells in the Intestinal Germinal Center of Patients With Inflammatory Bowel Disease

Abstract

Objective: This study aimed to investigate the effect of interleukin (IL)-21 and B cell lymphoma protein-6 on germinal center follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells and its relationship with the clinical features of inflammatory bowel disease (IBD).Methods: The expression of peripheral blood cytokines IL-21 and Bcl-6 mRNA was detected by reverse transcription–polymerase chain reaction. The distribution characteristics of Tfh and Tfr cells were detected using the triple immunofluorescence staining analysis.Results: The expression of IL-21 and Bcl-6 mRNA was upregulated in the ulcerative colitis (UC) and Crohn disease (CD) groups compared with that in the control group. Triple immunofluorescence staining showed that the number of Tfh cells in the intestinal germinal center obviously increased in the UC and CD groups compared with that in the control group, whereas the number of Tfr cells reduced.Conclusion: This study suggested that the Tfr and Tfh cells might be involved in the regulation of IBD. Bcl-6 and IL-21 can regulate the Tfh/Tfr ratio in the intestinal germinal center, promoting the occurrence and development of IBD.

The Role of T Follicular Helper Cells and Interleukin-21 in the Pathogenesis of Inflammatory Bowel Disease

“…The value of Mayo clinic score, erythrocyte sedimentation rate (ESR), or C-reactive protein (CRP) in UC patients was positively correlated with frequency of circulating Tfh cells [ 64 ]. Bcl-6 mRNA and Tfh cells in the germinal center were increased in the UC groups compared with that in the control group [ 65 ]. Recent studies further showed that Tfh cells were significantly increased in active UC patients compared with stable remission UC patients and healthy controls.…”

“…The value of the Mayo clinic score, erythrocyte sedimentation rate (ESR), or C-reactive protein (CRP) in UC patients was negatively correlated with circulating Tfr cells and Tfr/Tfh ratio [ 64 ]. The number of Tfr cells was also reduced in the intestinal germinal center of the UC groups compared with that of the control group [ 65 ]. Recent studies further showed that circulating Tfr was decreased in active UC patients compared with stable remission UC patients and healthy controls and Tfr was negatively correlated with serum IgG, circulating new memory B cells, plasmablasts, and clinical characteristics [ 66 ].…”

“…The level of IL-21 is elevated in UC patients compared to healthy controls [ 64 , 65 , 71 , 75 ]. Serum IL-21 was significantly higher in active UC compared with HC and stable remission UC patients [ 66 ].…”

“…The percentage of circulating Tfh cells in peripheral blood was significantly elevated in CD patients than in controls, and the percentage of circulating Tfh was significantly increased in penetrating CD compared with inflammatory CD or stricturing CD [ 82 ]. The number of Tfh cells was increased, and the number of Tfr cells was decreased in the intestinal germinal center of the CD groups compared with that of the control group [ 65 ]. Another study also reported that the percentage of IL-21-positive Tfh cells was higher in CD patients than in controls [ 77 ].…”

“…IL-21R was significantly highly expressed in the intestine from patients with CD compared with that in controls [ 78 ]. The expression of IL-21 was upregulated in the CD group compared with that in the control group [ 65 , 75 , 79 ].…”