IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential

Zhu, Shu; Qian, Youcun

doi:10.1042/cs20110496

Cited by 245 publications

(179 citation statements)

References 280 publications

(363 reference statements)

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“…Zauważono, że myszy z niedoborem IL-12p40 oraz IL-23p19 są odporne na eksperymentalnie wywoła-ne autoimmunologiczne zapalenia mózgu i rdzenia, natomiast myszy z brakiem podjednostki IL-12p35 rozwijają ciężką postać choroby. Jest to bezsprzeczny dowód na rolę Th17 w rozwoju zaburzeń autoimmunologicznych [24,30].…”

Section: Rola Czynników Genetycznych I Epigenetycznychunclassified

“…Komórki te są o wiele bardziej skuteczne w indukowaniu zapalenia niż limfocyty Th1, uznawane do tej pory za "głównego sprawcę" chorób autoimmunologicznych. Limfocyty Th17 są zaangażowane także w patogenezę chorób alergicz-nych poprzez przyczynianie się do aktywacji i rekrutacji neutrofilów [30,32].…”

Section: Rola Czynników Genetycznych I Epigenetycznychunclassified

“…Interleukina 17, oprócz kluczowej roli w obronie przeciwbakteryjnej i przeciwgrzybiczej, w otyłości i nowotworach, ma znaczenie w patogenezie chorób autoimmunologicznych [30]. Zwiększoną ilość Th17 oraz IL-17 i IL-23 w surowicy stwierdzono u niektó-rych pacjentów z toczniem rumieniowatym ukła-dowym.…”

Section: Rola Czynników Genetycznych I Epigenetycznychunclassified

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Psoriasis as an autoimmune disease

Owczarczyk‐Saczonek¹,

Placek²

2014

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StreSzczenieObecnie uważa się, że łuszczyca należy do kręgu schorzeń autoimmunologicznych, współistniejących z innymi chorobami z tej grupy. U pacjentów stwierdza się najczęściej łuszczycowe zapalenie stawów, reumatoidalne zapalenie stawów, choroby tkanki łącznej, stwardnienie rozsiane, autoimmunologiczne choroby tarczycy, celiakię, nieswoiste zapalenia jelit. Współwystępowanie tych zaburzeń może stanowić problem diagnostyczny i leczniczy (kontrowersje dotyczące stosowania kortykosteroidów). Wspólna patogeneza pozostaje nadal nie do końca wyjaśniona. Uważa się, że utrata immunotolerancji prowadzi do powstania m.in. autoreaktywnych limfocytów Th1 i Th17, które rozpoznają autoantygeny i prowadzą do ich niszczenia w danym narządzie docelowym. Pewne cechy mechanizmów immunologicznych obserwowanych w łuszczycy sugerują jej autoimmunologiczne tło. Należą do nich uwarunkowania genetyczne, np. PSORS 3 na chromosomie 4q predysponuje do celiakii, cukrzycy typu 1, choroby Gravesa-Basedowa i reumatoidalnego zapalenia stawów. Łuszczyca jest chorobą, w któ-rej decydującą rolę odgrywa aktywacja osi IL-12/Th1/IFN-γ i Th17/ IL-23. Prawdopodobnie IL-12 działa na naiwne limfocyty T i zapocząt-kowuje odpowiedź Th1, a IL-23 podtrzymuje reakcję zapalną mediowaną przez Th1, pobudza dojrzewanie i aktywność Th17 oraz wpływa na utrzymanie odpowiedniej puli komórek pamięci. Dochodzi również do zaburzenia funkcji limfocytów Treg, odpowiedzialnych za niszczenie limfocytów autoreaktywnych. Ponadto keratynocyty łuszczycowe mają zwiększoną oporność na apoptozę, której zadaniem jest eliminacja uszkodzonych komórek, aby nie zostały rozpoznane jako antygenowo obce. Badacze sugerują jednak, że początkowo następuje poliklonalna aktywacja limfocytów T wywołana przez superantygeny (m.in. paciorkowcowe białka M, peptydoglikan) lub uraz naskórka (objaw Köbne-ra), natomiast w późniejszej fazie autoreaktywne limfocyty T rozpoznają autoantygeny (keratyna 17, białka kapsydu L1 HPV 5, Pso p27) w naskórku, co prowadzi do reakcji autoimmunologicznej. AbStrActNowadays it is known that psoriasis belongs to the group of autoimmune diseases and may coexist with other diseases in this group. Most often patients have psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid diseases and multiple sclerosis. The coexistence of these disorders can be a diagnostic and therapeutic problem (there is controversy over the use of corticosteroids). The common pathogenesis is still not explained. We know that the loss of immunotolerance leads to formation of autoreactive Th1 and Th17 lym-

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Section: Rola Czynników Genetycznych I Epigenetycznychunclassified

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Psoriasis as an autoimmune disease

Owczarczyk‐Saczonek¹,

Placek²

2014

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“…IL-17 and TNF-α can act synergistically with each other and are involved in systemic inflammation [53][54][55] IL-17 can recruit monocytes, neutrophils and T-helper cells to the site of inflammation [56]and TNF-α is predominantly produced by macrophages, CD4 + lymphocytes, NK cells, and neurons [57]. TNF-α was found to be present in increased levels when human hepatic cells were infected with HCV and HIV-1 in vitro, and this effect was further exacerbated in the presence of morphine [58].…”

Section: Discussionmentioning

confidence: 99%

Coinfection with Hepatitis C Virus among HIV-1-Infected Individuals Increases Proinflammatory Cytokines and HIV-1 Disease Severity

Wigdahl¹

2016

MOJI

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Submit Manuscript | http://medcraveonline.com infection that is spontaneously cleared [3].However, in cases of HIV-1 and HCV coinfection, the number of chronic HCV infections rises to 90% [4]. The result of any viral infection depends on the interplay between the activation of host cellular factors to the infection and the viral mechanisms that counteract them [5]. HCV is responsible for activating antiviral interferon (IFN)-α/β expression, but irrespective of the expression of these cytokines, HCV can still replicate within the liver [6]. This could be due to the fact that the nonstructural proteins, nonstructural protein (NS)3 and NS5A, and the structural protein E2 can block the expression as well as transcription of IFN-α/β genes. Also, the NS5A protein induces expression of interleukin (IL)-8, associated with IFN-α inhibition [7] HCV can also block the antiviral action of natural killer (NK) and NKT cells thus hindering the expression of IFN-γ (an antiviral cytokine) due to the interaction between E2 and NK-cell CD81 molecule [8]. The production of cytokines by dendritic cells (DCs) is particularly affected by chronic HCV infection and there are contradictory reports concerning the expression of Th1 cytokines, with some studies suggesting that a Th1 response is suppressed [9] and some studies suggesting a progressive liver injury during chronic HCV has been associated with an increase in the Th1 responseassociated cytokines [10]. In this regard, HCV CD4 + T cells also play an important role in providing an adaptive response by activating cytotoxic and humoral responses. This can involve the secretion AbstractHIV-1, along with hepatitis B and C viruses (HBV and HCV), are known to share similar routes of transmission, including intravenous drug use, blood transfusions, sexual intercourse, and perinatal exposure. Thus, coinfection with HIV-1 and HBV or HCV is common. HIV-1 impacts the natural course of HBV and HCV infection by accelerating the progression of HBV/HCV-associated liver disease toward endstage cirrhosis and quantitative depletion of the CD4+ T-cell compartment. HBV or HCV coinfection with HIV-1 has also been associated with increased mortality when compared to either infection alone. In particular, we focus on the impact of coinfection with HCV on the HIV-1 pathogenic process in patients in the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort. Comparing HIV-1 mono-infection with HIV-1/HCV coinfection allows defining the detrimental effect of HCV coinfection as it relates to viral pathogenesis, disease progression, and the associated immune response during the course of this complex interplay, in the background of drug abuse, which is an important risk factor to both HIV-1 and HCV infection and on HIV-1 disease severity. The uniqueness of this study includes the fact that the patients are part of a cohort of HIV-1-infected individuals whose drug histories have been recorded longitudinally.

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“…IL-17 is a key regulatory cytokine secreted by innate immune cell types and has been shown to facilitate clearance of extracellular bacteria and fungus (21). Its dysregulation results in excessive inflammation, leading to tissue damage, chronic inflammation (22), autoimmunity (23), and chronic graft-versus-host disease in higher vertebrates (24). In a number of invertebrate species, IL-17 genes have been identified (21,25).…”

Section: Significancementioning

confidence: 99%

Developmental cell death programs license cytotoxic cells to eliminate histocompatible partners

Corey

Rosental

Kowarsky

et al. 2016

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

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In a primitive chordate model of natural chimerism, one chimeric partner is often eliminated in a process of allogeneic resorption. Here, we identify the cellular framework underlying loss of tolerance to one partner within a natural Botryllus schlosseri chimera. We show that the principal cell type mediating chimeric partner elimination is a cytotoxic morula cell (MC). Proinflammatory, developmental cell death programs render MCs cytotoxic and, in collaboration with activated phagocytes, eliminate chimeric partners during the "takeover" phase of blastogenic development. Among these genes, the proinflammatory cytokine IL-17 enhances cytotoxicity in allorecognition assays. Cellular transfer of FACS-purified MCs from allogeneic donors into recipients shows that the resorption response can be adoptively acquired. Transfer of 1 × 10 5 allogeneic MCs eliminated 33 of 78 (42%) recipient primary buds and 20 of 76 (20.5%) adult parental adult organisms (zooids) by 14 d whereas transfer of allogeneic cell populations lacking MCs had only minimal effects on recipient colonies. Furthermore, reactivity of transferred cells coincided with the onset of developmental-regulated cell death programs and disproportionately affected developing tissues within a chimera. Among chimeric partner "losers," severe developmental defects were observed in asexually propagating tissues, reflecting a pathologic switch in gene expression in developmental programs. These studies provide evidence that elimination of one partner in a chimera is an immune cell-based rejection that operates within histocompatible pairs and that maximal allogeneic responses involve the coordination of both phagocytic programs and the "arming" of cytotoxic cells.T he colonial marine species, Botryllus schlosseri, offers a unique platform to study mechanisms underlying loss of tolerance in a natural model system. Colonies undergo a genetically controlled histocompatibility reaction that can result in vascular fusion of distinct genotypes, creating a chimera (1, 2). Natural history studies among fused colonies show that partners rarely exist as stable chimeras (3-7). One chimeric partner is often eliminated in a process of allogeneic resorption, suggesting a break in immunological nonreactivity. Moreover, the eliminated partner may still persist, and even parasitize the nonresorbed partner, but at the level of the cell lineage (8, 9). Insight has been gained into fusion-partner resorption from observational studies showing physical similarities with the developmental period known as "takeover," or blastogenic stage D (4, 10). B. schlosseri colonies are composed of clonogenic individuals, termed "zooids," that undergo weekly cycles of death and regeneration, culminating in a massive wave of programmed cell death and removal, or takeover (11). These studies support the involvement of activated phagocytes in the elimination of tissues of the "losing" partner.Here, we study the progression by which fused colonies eliminate chimeric partners and show that partner eliminatio...

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IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential

Cited by 245 publications

References 280 publications

Psoriasis as an autoimmune disease

Psoriasis as an autoimmune disease

Coinfection with Hepatitis C Virus among HIV-1-Infected Individuals Increases Proinflammatory Cytokines and HIV-1 Disease Severity

Developmental cell death programs license cytotoxic cells to eliminate histocompatible partners

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