The Th17/IL-23 Axis and Natural Immunity in Psoriatic Arthritis

Maeda, Shinji; Hayami, Yoshihito; Naniwa, Taio; Ueda, Ryuzo

doi:10.1155/2012/539683

Cited by 43 publications

(40 citation statements)

References 72 publications

(77 reference statements)

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“…Based on the large number of IFN-γ-producing cells found in cutaneous eruptions, Ps and PsA were earlier classified as Th1 cell-mediated diseases, but recent studies suggested a crucial role for Th17 cells (11). Clearly, an immune response to yeast is dependent on Th17 (IL-23/IL-17A) pathway (24).…”

Section: Discussionmentioning

confidence: 99%

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Mannan induces ROS-regulated, IL-17A–dependent psoriasis arthritis-like disease in mice

Khmaladze

Kelkka

Guérard

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

121

168

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Significance We identified a previously undescribed disease mechanism for psoriasis (Ps) and psoriasis arthritis (PsA)-like disease by developing a new mouse model having characteristic features similar to those of Ps and PsA in human patients. Mannan-induced activation of tissue macrophages triggers IL-17A secretion from γδ T cells, causing Ps-like inflammation. Such inflammation was significantly increased under a reduced oxidative environment. Increased frequency of monocytes/macrophages, depletion experiments, and the disease suppressor function of macrophage-derived reactive oxygen species clearly argue in favor of a role for monocytes/macrophages in this disease model, which is in accordance with the findings in patients with the psoriatic form of skin lesions and arthritis. This novel PsA model could be immensely useful to test new therapeutics for patients with Ps and PsA.

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Section: Discussionmentioning

confidence: 99%

“…Although Ps and PsA were earlier categorized as T helper (Th) 1 cell-mediated diseases, later studies demonstrated the significance of Th17 cells in disease pathology (11,12). Nishimoto et al (13) proposed that Th17 cells carrying T-cell receptor (TCR) recognizing epidermal autoantigen could induce IL-17-dependent Ps-like skin inflammation in mice.…”

mentioning

confidence: 99%

Mannan induces ROS-regulated, IL-17A–dependent psoriasis arthritis-like disease in mice

Khmaladze

Kelkka

Guérard

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

121

168

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“…Th17 cells are a distinct T cell subset involved in autoimmune disease (32,33,(35)(36)(37). IL-17 enhances production of inflammatory cytokines and chemokines from RA synoviocytes (38).…”

Section: Discussionmentioning

confidence: 99%

Necessity of Lysophosphatidic Acid Receptor 1 for Development of Arthritis

Miyabe

Iwai

et al. 2013

Arthritis & Rheumatism

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Objective. Lysophosphatidic acid (LPA) is a bioactive lipid that binds to a group of cell surface G protein-coupled receptors (LPA receptors 1-6 [LPA 1-6 ]) and has been implicated as an important mediator of angiogenesis, inflammation, and cancer growth. This study was undertaken to analyze the effects of LPA 1 on the development of arthritis.Methods. Expression of LPA receptors on synovial tissue was analyzed by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. The effects of abrogation of LPA 1 on collageninduced arthritis (CIA) were evaluated using LPA 1 -deficient mice or LPA 1 antagonist. Migrating fluorescence-labeled CD11b؉ splenocytes, which were transferred into the synovium of mice with CIA, were counted. CD4؉ naive T cells were incubated under Th1-, Th2-, or Th17-polarizing conditions, and T helper cell differentiation was assessed. Osteoclast formation from bone marrow cells was examined.Results. LPA 1 was highly expressed in the synovium of patients with rheumatoid arthritis (RA) compared with that of patients with osteoarthritis. LPA 1 -deficient mice did not develop arthritis following immunization with type II collagen (CII). LPA 1 antagonist also ameliorated murine CIA. Abrogation of LPA 1 was associated with reductions in cell infiltration, bone destruction in the joints, and interleukin-17 production from CII-stimulated splenocytes. Infiltration of transferred CD11b؉ macrophages from LPA 1 -deficient mice into the synovium was suppressed compared with infiltration of macrophages from wild-type mice. LPA 1 antagonist inhibited the infiltration of macrophages from wild-type mice. Differentiation into Th17, but not Th1 or Th2, and osteoclast formation were also suppressed under conditions of LPA 1 deficiency or LPA 1 inhibition in vitro.Conclusion. Collectively, these results indicate that LPA/LPA 1 signaling contributes to the development of arthritis via cellular infiltration, Th17 differentiation, and osteoclastogenesis. Thus, LPA 1 may be a promising target molecule for RA therapy.Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammatory cell infiltration and bone destruction at multiple joints. The inflammation process in RA leads to synovial hyperplasia with proliferation of fibroblast-like synoviocytes (FLS), angiogenesis, and infiltration of inflammatory cells, including lymphocytes and macrophages (1,2).

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“…PsA has long been considered as a Th1-mediated disease, with interferon (IFN)-g and IL-12 as signature cytokines [43]. Recently, however, it has been shown that both innate and adaptive immunity, leading to the activation of the IL-23/Th17 axis, may contribute to the initiation of tissue inflammation [44][45][46]. More recently, IL-9 has been also demonstrated to be involved in the pathogenesis of psoriasis [47].…”

Section: Il-9 and Th9 Cells In Psoriatic Arthritismentioning

confidence: 99%

Interleukin-9 and T helper type 9 cells in rheumatic diseases

Ciccia

Guggino

Ferrante

et al. 2016

Clinical and Experimental Immunology

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SummaryInterleukin (IL)-9 is a 28-30 kDa monomeric glycosylated polypeptide belonging to the IL-7/IL-9 family of proteins that bind to a composite receptor consisting of the private receptor IL-9R and the IL-2 receptor, gamma (IL-2RG), a common gamma subunit shared by the receptors of many different cytokines. The IL-9R is expressed widely and IL-9 impacts a number of effector cells, such as effector T cells, B cells, innate lymphoid cells, mast cells, polymorphonuclear cells, epithelial cells and smooth muscle cells, playing an important role in regulating inflammatory immunity. The critical role of IL-9 in promoting cellular and humoral immune responses makes it an important focus of potential therapeutic interventions. Recently, a defined subset of T helper type cells, Th9 cells, has been identified by the potent production of IL-9. The involvement of the Th9 cell subset has been described in many types of inflammatory diseases, namely atopic diseases, helminth infections, experimental autoimmune encephalomyelitis and ulcerative colitis. In this review, we summarize the IL-9 biological activities, highlighting roles for IL-9 and Th9 cells in rheumatoid and psoriatic arthritis, systemic vasculitis, systemic lupus erythematosus and systemic sclerosis.

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The Th17/IL-23 Axis and Natural Immunity in Psoriatic Arthritis

Cited by 43 publications

References 72 publications

Mannan induces ROS-regulated, IL-17A–dependent psoriasis arthritis-like disease in mice

Mannan induces ROS-regulated, IL-17A–dependent psoriasis arthritis-like disease in mice

Necessity of Lysophosphatidic Acid Receptor 1 for Development of Arthritis

Interleukin-9 and T helper type 9 cells in rheumatic diseases

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