학술논문
Retinoic Acid Is Elevated in the Mucosa of Patients With Active Ulcerative Colitis and Displays a Proinflammatory Role by Augmenting IL-17 and IFN[gamma] Production
Original Research Article--Basic Science
Original Research Article--Basic Science
Document Type
Academic Journal
Author
Source
Inflammatory Bowel Diseases. January 2021, Vol. 27 Issue 1, p74, 10 p.
Subject
Language
English
ISSN
1078-0998
Abstract
INTRODUCTION A remarkable attribute of the normal gastrointestinal tract is that the mucosal immune system is always poised to respond against ingested pathogens but is unresponsive to normal intestinal microflora. [...]
Background: All-trans retinoic acid (RA) plays a crucial role in promoting [Foxp3.sup.+] Treg generation while reciprocally inhibiting Th1/Th17 generation. Our previous research highlighted that in the face of inflammatory conditions, RA plays a contrary role where it aggravates intestinal inflammation by promoting interferon (IFN)[gamma] and interleukin (IL)-17 differentiation in vitro. Methods: In this study we translated our in vitro results into a clinical setting where we estimated mucosal and serum RA levels along with the immunophenotypic profile (IL-17, IFN[gamma], Foxp3, IL-10) in adaptive (CD4, CD8) and innate-like T cells (mucosal associated invariant T cells and [gamma][delta] T cells) in patients with ulcerative colitis in remission or with active inflammation. Results: This is the first study to estimate RA levels in the human gut and shows that patients with active disease had increased mucosal RA levels as compared with patients in remission (4.0 vs 2.5 ng/mL; P < 0.01) and control patients (3.4 vs 0.8 ng/mL; P < 0.0001). This effect was accompanied by significantly elevated IL-17 and IFN[gamma] in tissue [CD4.sup.+], [CD8.sup.+], mucosal associated invariant [T.sup.+] cells, and [gamma][[delta].sup.+] T cells. Moreover, the raised RA levels in patients with active disease showed a positive correlation with proinflammatory cytokines (IL- 17, IFN[gamma]) and a negative correlation with IL-10. We also found that RA negatively correlated with IL-9, thereby reinstating our previous finding that RA inhibits Th9 differentiation. Conclusions: These data confirm our previous in vitro results that in the presence of inflammation, RA plays a crucial role in maintaining gut inflammation by upregulating proinflammatory markers. Key Words: retinoic acid, ulcerative colitis, vitamin A, inflammation, adaptive immunity
Background: All-trans retinoic acid (RA) plays a crucial role in promoting [Foxp3.sup.+] Treg generation while reciprocally inhibiting Th1/Th17 generation. Our previous research highlighted that in the face of inflammatory conditions, RA plays a contrary role where it aggravates intestinal inflammation by promoting interferon (IFN)[gamma] and interleukin (IL)-17 differentiation in vitro. Methods: In this study we translated our in vitro results into a clinical setting where we estimated mucosal and serum RA levels along with the immunophenotypic profile (IL-17, IFN[gamma], Foxp3, IL-10) in adaptive (CD4, CD8) and innate-like T cells (mucosal associated invariant T cells and [gamma][delta] T cells) in patients with ulcerative colitis in remission or with active inflammation. Results: This is the first study to estimate RA levels in the human gut and shows that patients with active disease had increased mucosal RA levels as compared with patients in remission (4.0 vs 2.5 ng/mL; P < 0.01) and control patients (3.4 vs 0.8 ng/mL; P < 0.0001). This effect was accompanied by significantly elevated IL-17 and IFN[gamma] in tissue [CD4.sup.+], [CD8.sup.+], mucosal associated invariant [T.sup.+] cells, and [gamma][[delta].sup.+] T cells. Moreover, the raised RA levels in patients with active disease showed a positive correlation with proinflammatory cytokines (IL- 17, IFN[gamma]) and a negative correlation with IL-10. We also found that RA negatively correlated with IL-9, thereby reinstating our previous finding that RA inhibits Th9 differentiation. Conclusions: These data confirm our previous in vitro results that in the presence of inflammation, RA plays a crucial role in maintaining gut inflammation by upregulating proinflammatory markers. Key Words: retinoic acid, ulcerative colitis, vitamin A, inflammation, adaptive immunity