Imperial College London


Faculty of MedicineNational Heart & Lung Institute

Reader in Leukocyte Biology



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BibTex format

author = {Blazek, K and Eames, HL and Weiss, M and Byrne, AJ and Perocheau, D and Pease, JE and Doyle, S and McCann, F and Williams, RO and Udalova, IA},
doi = {10.1084/jem.20140995},
journal = {Journal of Experimental Medicine},
pages = {845--853},
title = {IFN-lambda resolves inflammation via suppression of neutrophil infiltration and IL-1 beta production},
url = {},
volume = {212},
year = {2015}

RIS format (EndNote, RefMan)

AB - The most studied biological role of type III interferons (IFNs) has so far been their antiviral activity, but their role in autoimmune and inflammatory diseases remains largely unexplored. Here, we show that treatment with IFN-λ2/IL-28A completely halts and reverses the development of collagen-induced arthritis (CIA) and discover cellular and molecular mechanisms of IL-28A antiinflammatory function. We demonstrate that treatment with IL-28A dramatically reduces numbers of proinflammatory IL-17–producing Th17 and γδ T cells in the joints and inguinal lymph nodes, without affecting T cell proliferative responses or levels of anticollagen antibodies. IL-28A exerts its antiinflammatory effect by restricting recruitment of IL-1b–expressing neutrophils, which are important for amplification of inflammation. We identify neutrophils as cells expressing high levels of IFN-λ receptor 1 (IFNLR1)–IL-28 receptor α (IL28RA) and targeted by IL-28A. Our data highlight neutrophils as contributors to the pathogenesis of autoimmune arthritis and present IFN-λs or agonists of IFNLR1–IL28RA as putative new therapeutics for neutrophil-driven inflammation.IFN-λ1, -λ2, and -λ3 (or IL-29, IL-28A, and IL-28B, respectively) are members of the class II cytokine family evolutionarily related to both IL-10 and type I IFNs (IFN-α/β), and are collectively referred to as type III IFNs. IFN-λ1 (IL-29) is the main cytokine of this family produced in human cells, but it is not expressed in mice, where IL-28A/B play the major role. Despite the use of a distinct receptor complex, IFNLR1–IL28RA activates similar signaling pathways to that of the type I IFN receptor (Kotenko et al., 2003; Sheppard et al., 2003), and the most studied biological role of IFN-λs has so far been their antiviral activity. However, there is evidence to suggest that they may also have pleiotropic immune functions. IF
AU - Blazek,K
AU - Eames,HL
AU - Weiss,M
AU - Byrne,AJ
AU - Perocheau,D
AU - Pease,JE
AU - Doyle,S
AU - McCann,F
AU - Williams,RO
AU - Udalova,IA
DO - 10.1084/jem.20140995
EP - 853
PY - 2015///
SN - 0022-1007
SP - 845
TI - IFN-lambda resolves inflammation via suppression of neutrophil infiltration and IL-1 beta production
T2 - Journal of Experimental Medicine
UR -
UR -
UR -
VL - 212
ER -