Interleukin-21: a critical regulator of the balance between effector and regulatory T-cell responses

Monteleone, Giovanni; Pallone, Francesco; MacDonald, Thomas T.

doi:10.1016/j.it.2008.02.008

Cited by 82 publications

(77 citation statements)

References 50 publications

(86 reference statements)

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“…All IL-17-secreting cells derived from NTreg cosecreted TNF-α, also highly proinflammatory. Some of them cosecreted IL-21 and IL-22, two cytokines that have been described as T H 17 associated, although not exclusively secreted by T H 17 cells (41)(42)(43)(44). IL-17F is a proinflammatory cytokine with functions initially reported as similar to those of IL-17A and sharing the same receptor (45).…”

Section: Discussionmentioning

confidence: 99%

Human RORγt ⁺ T _H 17 cells preferentially differentiate from naive FOXP3 ⁺ Treg in the presence of lineage-specific polarizing factors

Valmori

Raffin

Raimbaud

et al. 2010

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

142

117

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RORγt + T H 17 cells are a proinflammatory CD4 + T-cell population associated with autoimmune tissue injury. In mice, priming of T H 17 requires TGF-β, which alone directs the priming of FOXP3 + regulatory T cells (Treg), in association with inflammatory cytokines. Priming of human T H 17 cells from conventional naive CD4 + T cells under similar conditions, however, has proved difficult to achieve. Here, we report that differentiation of human T H 17 cells preferentially occurs from FOXP3 + naive Treg (NTreg) in the presence of IL-2 and IL-1β and is increased by IL-23 and TGF-β. IL-1β-mediated differentiation correlated with IL-1RI expression in stimulated NTreg and was accompanied by induction of RORγt along with down-regulation of FOXP3. IL-17-secreting cells in NTreg cultures cosecreted TNF-α and IL-2 and contained distinct subpopulations cosecreting or not cosecreting IFN-γ and other T H 17-associated cytokines. Polarized NTreg contained significant subpopulations of CCR6-expressing cells that were highly enriched in IL-17-secreting cells. Finally, analysis of CCR6 expression with respect to that of IL-1RI identified distinct IL-17-secreting subpopulations that had maintained or lost their suppressive functions. Together our results support the concept that priming of human T H 17 from naive CD4 + T cells preferentially takes place from FOXP3 + Treg precursors in the presence of lineage-specific polarizing factors.IL-1 | IL-17 | IL-23 | TGF-β | CD4 T cells

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Section: Discussionmentioning

confidence: 99%

Human RORγt ⁺ T _H 17 cells preferentially differentiate from naive FOXP3 ⁺ Treg in the presence of lineage-specific polarizing factors

Valmori

Raffin

Raimbaud

et al. 2010

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

142

117

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“…Znaczenie IL-23 w patogenezie łuszczycy potwierdzono eksperymentalnie: podanie śródskórne myszom indukuje zmiany chorobowe [34]. Terapie ukierunkowane na IL-23 redukują zmiany łuszczycowe, a niektórzy autorzy sugerują, że neutralizacja IL-21 za pomocą rozpuszczalnych receptorów lub przeciwciał monoklonalnych może wzmacniać efekt leczenia [35]. Również stężenie IL-22 jest zwiększone u pacjentów z łuszczycą i skorelowane z ciężkością choroby [17,34].…”

Section: Rola Czynników Genetycznych I Epigenetycznychunclassified

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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“…+ and CD8 + T cells, induces the genes encoding IL-12R, IL-18R, IFN-g, IL-2R and the Th1-associated transcription factor T-bet in activated memory T cells, drives the differentiation of B cells into memory cells and immunoglobulin (Ig)-secreting plasma cells and promotes the activity of natural killer (NK) cells [11]. Moreover, IL-21 enhances T follicular helper cell and Th17 cell differentiation, downregulates the induction of T regulatory cells and controls the activity of non-immune cells, including epithelial cells and stromal cells [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, IL-21 enhances T follicular helper cell and Th17 cell differentiation, downregulates the induction of T regulatory cells and controls the activity of non-immune cells, including epithelial cells and stromal cells [9][10][11]. Evidence has shown that IL-21 is associated with the development of several autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and coeliac disease [11,12]. In recent years, IL-21 has been found to be involved in the pathogenesis of human IBD [13,14].…”

Section: Introductionmentioning

confidence: 99%

Anti-tumour necrosis factor therapy enhances mucosal healing through down-regulation of interleukin-21 expression and T helper type 17 cell infiltration in Crohn's disease

Liu

Xia

et al. 2013

Clinical and Experimental Immunology

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Interleukin-21: a critical regulator of the balance between effector and regulatory T-cell responses

Cited by 82 publications

References 50 publications

Human RORγt ⁺ T _H 17 cells preferentially differentiate from naive FOXP3 ⁺ Treg in the presence of lineage-specific polarizing factors

Human RORγt ⁺ T _H 17 cells preferentially differentiate from naive FOXP3 ⁺ Treg in the presence of lineage-specific polarizing factors

Psoriasis as an autoimmune disease

Anti-tumour necrosis factor therapy enhances mucosal healing through down-regulation of interleukin-21 expression and T helper type 17 cell infiltration in Crohn's disease

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Interleukin-21: a critical regulator of the balance between effector and regulatory T-cell responses

Cited by 82 publications

References 50 publications

Human RORγt + T H 17 cells preferentially differentiate from naive FOXP3 + Treg in the presence of lineage-specific polarizing factors

Human RORγt + T H 17 cells preferentially differentiate from naive FOXP3 + Treg in the presence of lineage-specific polarizing factors

Psoriasis as an autoimmune disease

Anti-tumour necrosis factor therapy enhances mucosal healing through down-regulation of interleukin-21 expression and T helper type 17 cell infiltration in Crohn's disease

Contact Info

Product

Resources

About

Human RORγt ⁺ T _H 17 cells preferentially differentiate from naive FOXP3 ⁺ Treg in the presence of lineage-specific polarizing factors

Human RORγt ⁺ T _H 17 cells preferentially differentiate from naive FOXP3 ⁺ Treg in the presence of lineage-specific polarizing factors