TY - JOUR
T1 - Shared and Distinct Functions of Type I and Type III Interferons
AU - Lazear, Helen M.
AU - Schoggins, John W.
AU - Diamond, Michael S.
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/4/16
Y1 - 2019/4/16
N2 - Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared signaling pathways, and transcriptional programs. However, recent discoveries have revealed context-specific functional differences. Here, we provide a comprehensive review of type I and type III IFN activities, highlighting shared and distinct features from molecular mechanisms through physiological responses. Beyond discussing canonical antiviral functions, we consider the adaptive immune priming, anti-tumor, and autoimmune functions of IFNs. We discuss a model wherein type III IFNs serve as a front-line defense that controls infection at epithelial barriers while minimizing damaging inflammatory responses, reserving the more potent type I IFN response for when local responses are insufficient. In this context, we discuss current therapeutic applications targeting these cytokine pathways and highlight gaps in understanding of the biology of type I and type III IFNs in health and disease.
AB - Type I interferons (IFNs) (IFN-α, IFN-β) and type III IFNs (IFN-λ) share many properties, including induction by viral infection, activation of shared signaling pathways, and transcriptional programs. However, recent discoveries have revealed context-specific functional differences. Here, we provide a comprehensive review of type I and type III IFN activities, highlighting shared and distinct features from molecular mechanisms through physiological responses. Beyond discussing canonical antiviral functions, we consider the adaptive immune priming, anti-tumor, and autoimmune functions of IFNs. We discuss a model wherein type III IFNs serve as a front-line defense that controls infection at epithelial barriers while minimizing damaging inflammatory responses, reserving the more potent type I IFN response for when local responses are insufficient. In this context, we discuss current therapeutic applications targeting these cytokine pathways and highlight gaps in understanding of the biology of type I and type III IFNs in health and disease.
UR - http://www.scopus.com/inward/record.url?scp=85063796827&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2019.03.025
DO - 10.1016/j.immuni.2019.03.025
M3 - Review article
C2 - 30995506
AN - SCOPUS:85063796827
SN - 1074-7613
VL - 50
SP - 907
EP - 923
JO - Immunity
JF - Immunity
IS - 4
ER -