TY - JOUR
T1 - Interferon Lambda in the Pathogenesis of Inflammatory Bowel Diseases
AU - Wallace, Jonathan W.
AU - Constant, David A.
AU - Nice, Timothy J.
N1 - Publisher Copyright:
© Copyright © 2021 Wallace, Constant and Nice.
PY - 2021/10/12
Y1 - 2021/10/12
N2 - Interferon λ (IFN-λ) is critical for host viral defense at mucosal surfaces and stimulates immunomodulatory signals, acting on epithelial cells and few other cell types due to restricted IFN-λ receptor expression. Epithelial cells of the intestine play a critical role in the pathogenesis of Inflammatory Bowel Disease (IBD), and the related type II interferons (IFN-γ) have been extensively studied in the context of IBD. However, a role for IFN-λ in IBD onset and progression remains unclear. Recent investigations of IFN-λ in IBD are beginning to uncover complex and sometimes opposing actions, including pro-healing roles in colonic epithelial tissues and potentiation of epithelial cell death in the small intestine. Additionally, IFN-λ has been shown to act through non-epithelial cell types, such as neutrophils, to protect against excessive inflammation. In most cases IFN-λ demonstrates an ability to coordinate the host antiviral response without inducing collateral hyperinflammation, suggesting that IFN-λ signaling pathways could be a therapeutic target in IBD. This mini review discusses existing data on the role of IFN-λ in the pathogenesis of inflammatory bowel disease, current gaps in the research, and therapeutic potential of modulating the IFN-λ-stimulated response.
AB - Interferon λ (IFN-λ) is critical for host viral defense at mucosal surfaces and stimulates immunomodulatory signals, acting on epithelial cells and few other cell types due to restricted IFN-λ receptor expression. Epithelial cells of the intestine play a critical role in the pathogenesis of Inflammatory Bowel Disease (IBD), and the related type II interferons (IFN-γ) have been extensively studied in the context of IBD. However, a role for IFN-λ in IBD onset and progression remains unclear. Recent investigations of IFN-λ in IBD are beginning to uncover complex and sometimes opposing actions, including pro-healing roles in colonic epithelial tissues and potentiation of epithelial cell death in the small intestine. Additionally, IFN-λ has been shown to act through non-epithelial cell types, such as neutrophils, to protect against excessive inflammation. In most cases IFN-λ demonstrates an ability to coordinate the host antiviral response without inducing collateral hyperinflammation, suggesting that IFN-λ signaling pathways could be a therapeutic target in IBD. This mini review discusses existing data on the role of IFN-λ in the pathogenesis of inflammatory bowel disease, current gaps in the research, and therapeutic potential of modulating the IFN-λ-stimulated response.
KW - Crohn’s disease (CD)
KW - inflammatory bowel disease (IBD)
KW - interferon lambda (IFN-λ)
KW - intestinal epithelial cell (IEC)
KW - ulcerative colitis (UC)
UR - http://www.scopus.com/inward/record.url?scp=85117968294&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85117968294&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.767505
DO - 10.3389/fimmu.2021.767505
M3 - Review article
C2 - 34712246
AN - SCOPUS:85117968294
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 767505
ER -