IL-26: An Emerging Proinflammatory Member of the IL-10 Cytokine Family with Multifaceted Actions in Antiviral, Antimicrobial, and Autoimmune Responses

Stephen-Victor, Emmanuel; Fickenscher, Helmut; Bayry, Jagadeesh

doi:10.1371/journal.ppat.1005624

Cited by 64 publications

(50 citation statements)

References 26 publications

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“…55 The IFN-like cytokines (IL-26 and IL-29) secreted by T17 cells also activate STAT1 in keratinocytes leading to the expression of CXCL9, CXCL10, and CXCL11 which attract Th1 cells into psoriatic skin and sensitize keratinocytes to its own action. 56, 57 Psoriatic keratinocytes also synthesize other growth factors which affect connective tissue cells in the dermis; platelet-derived growth factor (PDGF), angiopoietin-2, and vascular endothelial growth factor (VEGF) likely drive angiogenesis, which accounts for the erythematous skin lesions. 58 …”

Section: The Pivotal Role Of Il-17 In Updated Disease Models Of Psorimentioning

confidence: 99%

Psoriasis pathogenesis and the development of novel targeted immune therapies

Hawkes

Chan

Krueger

2017

Journal of Allergy and Clinical Immunology

709

605

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Psoriasis is caused by a complex interplay between the immune system, psoriasis-associated susceptibility loci, psoriasis autoantigens, and multiple environmental factors. Over the last two decades, research has unequivocally shown that psoriasis represents a bona fide T-cell mediated disease primarily driven by pathogenic T-cells that produce high levels of IL-17 in response to IL-23. The discovery of the central role for the IL-23/T17 cell axis in the development of psoriasis has led to a major paradigm shift in the pathogenic model for this condition. The activation and upregulation of IL-17 in pre-psoriatic skin produces a “feed forward” inflammatory response in keratinocytes that is self-amplifying and drives the development of mature psoriatic plaques by inducing epidermal hyperplasia, epidermal cell proliferation, and the recruitment of leukocyte subsets into the skin. Clinical trial data for monoclonal antibodies against IL-17 signaling (secukinumab, ixekizumab, and brodalumab) and newer IL-23p19 antagonists (tildrakizumab, guselkumab, and risankizumab) underscore the central role of these cytokines as predominant drivers of psoriatic disease. We are currently witnessing a translational revolution in the treatment and management of psoriasis. Emerging bispecific antibodies offer the potential for even better disease control, while small molecule drugs may offer future alternatives to the use of biologics and less costly long-term disease management.

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Section: The Pivotal Role Of Il-17 In Updated Disease Models Of Psorimentioning

confidence: 99%

Psoriasis pathogenesis and the development of novel targeted immune therapies

Hawkes

Chan

Krueger

2017

Journal of Allergy and Clinical Immunology

709

605

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“…immune responses (23)(24)(25)(26). We evaluated the levels of these molecules in the serum of 64 patients, to test whether pathogen-reactive neoplastic B cells are specifically associated with inflammation and infection.…”

Section: Patient Characteristics and Serological Statusmentioning

confidence: 99%

Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

Bosseboeuf¹,

Feron²,

Tallet³

et al. 2017

JCI Insight

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International audienceSubsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens. Antigen specificity of purified mc IgG from a large patient cohort (n = 244) was determined using a multiplex infectious-antigen array (MIAA), which screens for reactivity to purified antigens or lysates from 9 pathogens. Purified mc IgG from 23.4% of patients (57 of 244) specifically recognized 1 pathogen in the MIAA. EBV was the most frequent target (15.6%), with 36 of 38 mc IgGs recognizing EBV nuclear antigen-1 (EBNA-1). MM patients with EBNA-1-specific mc IgG (14.0%) showed substantially greater bone marrow plasma cell infiltration and higher β2-microglobulin and inflammation/infection-linked cytokine levels compared with other smoldering myeloma/MM patients. Five other pathogens were the targets of mc IgG: herpes virus simplex-1 (2.9%), varicella zoster virus (1.6%), cytomegalovirus (0.8%), hepatitis C virus (1.2%), and H. pylori (1.2%). We conclude that a dysregulated immune response to infection may underlie disease onset and/or progression of MGUS and MM for subsets of patients

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“…IL-22 can be co-expressed with interferon (IFN)-γ in Th1 cells and with IL-17A in Th17 cells [4, 8], however more recent studies identified Th22 cells, which only produce IL-22 but not IFN-γ or IL-17A [9, 10]. IL-26 is expressed only in humans but not in mice, and its main cellular sources include Th1 and Th17 cells, NK cells and alveolar macrophages [1, 11]. The biological effects of IL-20 subfamily plays a critical role in host defense, tissue protection and regulation of autoimmune response.…”

Section: Introductionmentioning

confidence: 99%

“…Among them, IL-22 is the most studied cytokine because it acts as the effector cytokine of Th17 and Th22 cells, as well as several lineages of innate lymphoid cells [4, 17, 18]. The biological functions and the association in human diseases of the broader IL-20 subfamily have been reviewed previously [1, 4, 11, 17, 19]. However, most of them only focus on IL-22, while the discussion on the roles of IL-20R cytokines in immunoregulation is limited.…”

Section: Introductionmentioning

confidence: 99%

IL-20 receptor cytokines in autoimmune diseases

Chen

Caspi

Chong

2018

Journal of Leukocyte Biology

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IL-19, IL-20, and IL-24 are the members of IL-10 family. They are also known as IL-20 receptor (IL-20R) cytokines as they all signal through the IL-20RA/IL-20RB receptor complex; IL-20 and IL-24 (but not IL-19) also signal through the IL-20RB/IL22RA1 receptor complex. Despite their protein structure homology and shared use of receptor complexes, they display distinct biological functions in immune regulation, tissue homeostasis, host defense, and oncogenesis. IL-20R cytokines can be expressed by both immune cells and epithelial cells, and are important for their interaction. In general, these cytokines are considered to be associated with pathogenesis of chronic inflammation and autoimmune diseases, including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. However, a number of studies also highlighted their suppressive functions in regulating both innate and adaptive T cell responses and other immune cells, suggesting that the role of IL-20R cytokines in autoimmunity may be complex. In this review, we will discuss the immunobiological functions of IL-20R cytokines and how they are involved in regulating autoimmune diseases.

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IL-26: An Emerging Proinflammatory Member of the IL-10 Cytokine Family with Multifaceted Actions in Antiviral, Antimicrobial, and Autoimmune Responses

Cited by 64 publications

References 26 publications

Psoriasis pathogenesis and the development of novel targeted immune therapies

Psoriasis pathogenesis and the development of novel targeted immune therapies

Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

IL-20 receptor cytokines in autoimmune diseases

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