New perspectives on effector mechanisms in uveitis

Luger, Dror; Caspi, Rachel R

doi:10.1007/s00281-008-0108-5

Cited by 87 publications

(97 citation statements)

References 50 publications

(67 reference statements)

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“…to B6 mice on the day of immunization. At 13 d postimmunization, uveitogenic T cells were isolated and restimulated with IRBP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and APCs under nonpolarizing conditions in the presence of Ag. As shown in Fig.…”

Section: Cl097-stimulated Dcs Enhance Irbp-specific Th17 Responses Anmentioning

confidence: 99%

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TLR7 Engagement on Dendritic Cells Enhances Autoreactive Th17 Responses via Activation of ERK

Xiao

Sun

et al. 2016

The Journal of Immunology

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In this study, we showed that TLR7 activation significantly promoted interphotoreceptor retinoid-binding protein (IRBP)-specific Th17 responses by upregulating RORγt, IL-17, GM-CSF, and IL-23R expression in experimental autoimmune uveitis mice. In vivo administration of CL097 activated dendritic cells (DCs) and endowed them with an increased ability to activate IRBP-specific Th17 cells. CL097-treated DCs (CL097-DCs) formed a cytokine milieu that favored the generation and maintenance of Th17 cells by stimulating IL-1β, IL-6, and IL-23 expression. Furthermore, IRBP-specific T cells from immunized mice injected with CL097-DCs produced more IL-17 and transferred more severe experimental autoimmune uveitis than did those from mice injected with DCs. The enhanced immunostimulatory activities of CL097-DCs depended on JNK, ERK, and p38 activation. Blockade of ERK, but not p38 or JNK, completely abolished the Th17 responses induced by CL097-DCs. Collectively, our findings suggest that CL097 treatment significantly promotes autoreactive IL-17+ T cell responses through enhancing DC activation, which is mediated, at least in part, via the activation of ERK signaling.

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Section: Cl097-stimulated Dcs Enhance Irbp-specific Th17 Responses Anmentioning

confidence: 99%

“…T helper 17 cells, induced by the master transcription factor RORgt, play a key role in the pathogenesis of many autoimmune diseases, including experimental autoimmune uveitis (EAU), an animal model of human uveitis (1)(2)(3). It is generally believed that IL-6 and TGF-b induce the differentiation of Th17 cells.…”

mentioning

confidence: 99%

TLR7 Engagement on Dendritic Cells Enhances Autoreactive Th17 Responses via Activation of ERK

Xiao

Sun

et al. 2016

The Journal of Immunology

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“…U pojedinim modelima eaU, upravo su one dominantan tip T-ćelija koji pokreće patološki proces, dok su u drugim modelima to prevashodno Th1 ćelije. Smatra se da na predominaciju Th1 ili Th17 ćelija u eaU, pored samog modela, utiče i kvalitet/kvantitet stimulacije receptora ćelija urođene imunosti i tip antigen-prezentujućih ćelija koje pokreću imunski odgovor (6,15). Ostaje otvoreno pitanje koje su ćelije, Th1 i Th17, presudne u razvoju uveitisa (6).…”

Section: Patogeneza Endogenih Uveitisa I Eksperimentalni Autoimunski unclassified

“…i nkT ćelije bi mogle da imaju patogenetsku ulogu delujući preko svojih produkata, il-17 i iFn-γ (6). antitela takođe mogu da, u slučaju kada je krvno-retinalna barijera već oštećena aktivnošću T-ćelija, doprinesu oštećenju oka (15).…”

Section: Patogeneza Endogenih Uveitisa I Eksperimentalni Autoimunski unclassified

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Role of cytokines in the pathogenesis of endogenous uveitis

Stanković¹,

Vučević²,

Kovačević-Pavićević³

et al. 2012

Medicinski casopis

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UVODUveitisi su grupa zapaljenjskih bolesti očiju, koje primarno zahvataju uvealni trakt (dužicu, cilijarno telo i sudovnjaču), mada se termin uveitis nekad koristi i u širem smislu, za zapaljenja koja pored uvealnog trakta zahvataju i retinu i optički nerv (1). Uveitisi se najčešće javljaju kod radno sposobne populacije, uzrasta od 20 do 50 godina. ređe se javljaju kod dece, ali su kod njih u čak 75% slučajeva praćeni komplikacijama (2, 3). komplikacije uveitisa mogu trajno oštetiti vid, te stoga uveitisi imaju veliki socio-ekonomsko-medicinski značaj (4). naime, uveitisi su uzrok slepila kod 10% slepih širom sveta i nalaze se na četvrtom mestu svih uzročnika slepila (4, 5).Prema poreklu uveitisi se dele na egzogene i endogene. egzogeni uveitisi nastaju posle povrede oka ili hirurške intervencije na oku kada patogeni agensi, najčešće bakterije ili gljivice prodru u njega (4). endogeni uveitisi mogu da budu udruženi sa drugim bolestima kao što su sarkoidoza, multipla skleroza, Behčetova bolest, Vogtkojanagi-Harada sindrom i juvenilni idiopatski artritis. Opisana je i udruženost endogenih uveitisa sa infekcijama, moguće usled sličnosti (molekulske mimikrije) između pojedinih komponenti mikroorganizama i struktura uvealnog trakta. Pored toga, endogeni uveitisi mogu biti i idiopatski. U osnovi endogenih uveitisa leže imunski mehanizmi, pri čemu imunski odgovor mogu da pokrenu kako strani, tako i sopstveni antigeni (npr. S-antigen) koji interleukin-4, interleukin-5, interleukin-12, interleukin-17, interleukin-23, interferon-gamma and other

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Suppression of Experimental Autoimmune Uveoretinitis by Regulatory Dendritic Cells in Mice

Usui

Takeuchi²,

Hattori³

et al. 2009

Arch Ophthalmol

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To examine the effects of bone marrowderived regulatory dendritic cells (DCs) with potent immunoregulatory properties on the development of experimental autoimmune uveoretinitis (EAU). Methods: Bone marrow cells obtained from C57BL/6 mice were treated with granulocyte-macrophage colonystimulating factor, transforming growth factor ␤, and interleukin (IL) 10 and stimulated with lipopolysaccharide to produce mature and regulatory DCs. Expression of major histocompatibility complex and costimulatory molecules was analyzed by flow cytometry. Then EAU was induced by immunization with human interphotoreceptor retinoid-binding protein (hIRBP) peptide 1-20, followed by intravenous injection of hIRBP peptidepulsed regulatory DCs. Control mice received transforming growth factor ␤ and IL-10 nontreated mature DC or phosphate-buffered saline. We evaluated EAU clinically and histopathologically. Immunologic responses to hIRBP peptide were assessed by delayed-type hypersensitivity and T-cell proliferation and cytokine production. Results: Regulatory DCs expressed comparable levels of major histocompatibility complex class II molecules but reduced levels of CD80, CD86, and CD40 compared with mature DCs. Delayed-type hypersensitivity to hIRBP peptide and the development of EAU were markedly suppressed in mice receiving regulatory DCs compared with control mice. Lymph node cells from regulatory DC-treated mice showed significantly reduced hIRBP-specific T-cell proliferation and interferon ␥ production but increased IL-10 production. Conclusion: Administration of regulatory DCs potentially inhibited the development of EAU. Clinical Relevance: Application of regulatory DCs may be a novel candidate for immunotherapy for human endogenous uveitis.

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New perspectives on effector mechanisms in uveitis

Cited by 87 publications

References 50 publications

TLR7 Engagement on Dendritic Cells Enhances Autoreactive Th17 Responses via Activation of ERK

TLR7 Engagement on Dendritic Cells Enhances Autoreactive Th17 Responses via Activation of ERK

Role of cytokines in the pathogenesis of endogenous uveitis

Suppression of Experimental Autoimmune Uveoretinitis by Regulatory Dendritic Cells in Mice

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