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Erschienen in: Seminars in Immunopathology 6/2019

07.10.2019 | Review

Resolution of uveitis

verfasst von: Gerhild Wildner, Maria Diedrichs-Möhring

Erschienen in: Seminars in Immunopathology | Ausgabe 6/2019

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Abstract

Autoimmune uveitis is a sight-threatening, rare disease, potentially leading to blindness. Uveitis is a synonym for intraocular inflammation, presenting as various clinical phenotypes with different underlying immune responses in patients, whereas different animal models usually represent one certain clinical and immunological type of uveitis due to genetic uniformity and the method of disease induction. T cells recognizing intraocular antigens initiate the disease, recruiting inflammatory cells (granulocytes, monocytes/macrophages) to the eyes, which cause the damage of the tissue. The treatment of uveitis so far aims at downregulation of inflammation to protect the ocular tissues from damage, and at immunosuppression to stop fueling T cell reactivity. Uveitis is usually prevented by specific mechanisms of the ocular immune privilege and the blood-eye-barriers, but once the disease is induced, mechanisms of the immune privilege as well as a variety of novel regulatory features including new Treg cell populations and suppressive cytokines are induced to downregulate the ocular inflammation and T cell responses and to avoid relapses and chronicity. Here we describe mechanisms of regulation observed in experimental animal models as well as detected in studies with peripheral lymphocytes from patients.
Literatur
1.
Zurück zum Zitat Rothova A, Suttorp van Schulten MS, Frits Treffers W, Kijlstra A (1996) Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol 80(4):332–336 Issn: 0007–1161CrossRefPubMedPubMedCentral Rothova A, Suttorp van Schulten MS, Frits Treffers W, Kijlstra A (1996) Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol 80(4):332–336 Issn: 0007–1161CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Jabs DA, Nussenblatt RB, Rosenbaum JT (2005) Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 140(3):509–516CrossRefPubMed Jabs DA, Nussenblatt RB, Rosenbaum JT (2005) Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 140(3):509–516CrossRefPubMed
3.
Zurück zum Zitat Singh VK, Kalra HK, Yamaki K, Abe T, Donoso LA, Shinohara T (1990) Molecular mimicry between a uveitopathogenic site of S-antigen and viral peptides. Induction of experimental autoimmune uveitis in Lewis rats. J Immunol (Baltimore, Md : 1950) 144(4):1282–1287 Singh VK, Kalra HK, Yamaki K, Abe T, Donoso LA, Shinohara T (1990) Molecular mimicry between a uveitopathogenic site of S-antigen and viral peptides. Induction of experimental autoimmune uveitis in Lewis rats. J Immunol (Baltimore, Md : 1950) 144(4):1282–1287
5.
Zurück zum Zitat Singh VK, Yamaki K, Donoso LA, Shinohara T (1989) Sequence homology between yeast histone H3 and uveitopathogenic site of S-antigen: lymphocyte cross-reaction and adoptive transfer of the disease. Cell Immunol 119(1):211–221CrossRefPubMed Singh VK, Yamaki K, Donoso LA, Shinohara T (1989) Sequence homology between yeast histone H3 and uveitopathogenic site of S-antigen: lymphocyte cross-reaction and adoptive transfer of the disease. Cell Immunol 119(1):211–221CrossRefPubMed
7.
Zurück zum Zitat Mochizuki M, Kuwabara T, McAllister C, Nussenblatt RB, Gery I (1985) Adoptive transfer of experimental autoimmune uveoretinitis in rats. Immunopathogenic mechanisms and histologic features. Invest Ophthalmol Vis Sci 26:1):1–1):9PubMed Mochizuki M, Kuwabara T, McAllister C, Nussenblatt RB, Gery I (1985) Adoptive transfer of experimental autoimmune uveoretinitis in rats. Immunopathogenic mechanisms and histologic features. Invest Ophthalmol Vis Sci 26:1):1–1):9PubMed
11.
Zurück zum Zitat Egwuagu CE, Yu C-R (2015) Interleukin 35-producing B cells (i35-Breg): a new mediator of regulatory B-cell functions in CNS autoimmune diseases. Crit Rev Immunol 35(1):49–57CrossRefPubMedPubMedCentral Egwuagu CE, Yu C-R (2015) Interleukin 35-producing B cells (i35-Breg): a new mediator of regulatory B-cell functions in CNS autoimmune diseases. Crit Rev Immunol 35(1):49–57CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Grégoire S, Terrada C, Martin GH, Fourcade G, Baeyens A, Marodon G, Fisson S, Billiard F, Lucas B, Tadayoni R, Béhar-Cohen F, Levacher B, Galy A, LeHoang P, Klatzmann D, Bodaghi B, Salomon BL (2016) Treatment of uveitis by in situ administration of ex vivo–activated polyclonal regulatory T cells. J Immunol 196(5):2109–2118. https://doi.org/10.4049/jimmunol.1501723 CrossRefPubMed Grégoire S, Terrada C, Martin GH, Fourcade G, Baeyens A, Marodon G, Fisson S, Billiard F, Lucas B, Tadayoni R, Béhar-Cohen F, Levacher B, Galy A, LeHoang P, Klatzmann D, Bodaghi B, Salomon BL (2016) Treatment of uveitis by in situ administration of ex vivo–activated polyclonal regulatory T cells. J Immunol 196(5):2109–2118. https://​doi.​org/​10.​4049/​jimmunol.​1501723 CrossRefPubMed
17.
18.
Zurück zum Zitat Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, Nussenblatt RB, Stiehm ER, Tessler H, Van Gelder RN, Whitcup SM, Yocum D (2000) Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol 130(4):492–513CrossRefPubMed Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, Nussenblatt RB, Stiehm ER, Tessler H, Van Gelder RN, Whitcup SM, Yocum D (2000) Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol 130(4):492–513CrossRefPubMed
24.
Zurück zum Zitat Fabiani C, Vitale A, Emmi G, Lopalco G, Vannozzi L, Guerriero S, Gentileschi S, Bacherini D, Franceschini R, Frediani B, Galeazzi M, Iannone F, Tosi GM, Cantarini L (2017) Interleukin (IL)-1 inhibition with anakinra and canakinumab in Behçet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol 36(1):191–197. https://doi.org/10.1007/s10067-016-3506-4 CrossRefPubMed Fabiani C, Vitale A, Emmi G, Lopalco G, Vannozzi L, Guerriero S, Gentileschi S, Bacherini D, Franceschini R, Frediani B, Galeazzi M, Iannone F, Tosi GM, Cantarini L (2017) Interleukin (IL)-1 inhibition with anakinra and canakinumab in Behçet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol 36(1):191–197. https://​doi.​org/​10.​1007/​s10067-016-3506-4 CrossRefPubMed
25.
Zurück zum Zitat Tappeiner C, Mesquida M, Adan A, Anton J, Ramanan AV, Carreno E, Mackensen F, Kotaniemi K, de Boer JH, Bou R, de Vicuna CG, Heiligenhaus A (2016) Evidence for tocilizumab as a treatment option in refractory uveitis associated with juvenile idiopathic arthritis. 43(12) (0315-162X (Print)):2183–2188 Tappeiner C, Mesquida M, Adan A, Anton J, Ramanan AV, Carreno E, Mackensen F, Kotaniemi K, de Boer JH, Bou R, de Vicuna CG, Heiligenhaus A (2016) Evidence for tocilizumab as a treatment option in refractory uveitis associated with juvenile idiopathic arthritis. 43(12) (0315-162X (Print)):2183–2188
26.
Zurück zum Zitat Calvo-Río V, Santos-Gómez M, Calvo I, González-Fernández MI, López-Montesinos B, Mesquida M, Adán A, Hernández MV, Maíz O, Atanes A, Bravo B, Modesto C, Díaz-Cordovés G, Palmou-Fontana N, Loricera J, González-Vela MC, Demetrio-Pablo R, Hernández JL, González-Gay MA, Blanco R (2017) Anti–interleukin-6 receptor tocilizumab for severe juvenile idiopathic arthritis–associated uveitis refractory to anti–tumor necrosis factor therapy: a multicenter study of twenty-five patients. Arthritis Rheum 69(3):668–675. https://doi.org/10.1002/art.39940 CrossRef Calvo-Río V, Santos-Gómez M, Calvo I, González-Fernández MI, López-Montesinos B, Mesquida M, Adán A, Hernández MV, Maíz O, Atanes A, Bravo B, Modesto C, Díaz-Cordovés G, Palmou-Fontana N, Loricera J, González-Vela MC, Demetrio-Pablo R, Hernández JL, González-Gay MA, Blanco R (2017) Anti–interleukin-6 receptor tocilizumab for severe juvenile idiopathic arthritis–associated uveitis refractory to anti–tumor necrosis factor therapy: a multicenter study of twenty-five patients. Arthritis Rheum 69(3):668–675. https://​doi.​org/​10.​1002/​art.​39940 CrossRef
28.
30.
Zurück zum Zitat Diedrichs-Möhring M, Leban J, Strobl S, Obermayr F, Wildner G (2015) A new small molecule for treating inflammation and chorioretinal neovascularization in relapsing-remitting and chronic experimental autoimmune uveitis: a new small molecule to treat monophasic and chronic EAU. Invest Ophthalmol Vis Sci 56(2):1147–1157. https://doi.org/10.1167/iovs.14-15518 CrossRef Diedrichs-Möhring M, Leban J, Strobl S, Obermayr F, Wildner G (2015) A new small molecule for treating inflammation and chorioretinal neovascularization in relapsing-remitting and chronic experimental autoimmune uveitis: a new small molecule to treat monophasic and chronic EAU. Invest Ophthalmol Vis Sci 56(2):1147–1157. https://​doi.​org/​10.​1167/​iovs.​14-15518 CrossRef
34.
Zurück zum Zitat Charukamnoetkanok P, Fukushima A, Whitcup SM, Gery I, Egwuagu CE (1998) Expression of ocular autoantigens in the mouse thymus. Curr Eye Res 17(8):788–792CrossRefPubMed Charukamnoetkanok P, Fukushima A, Whitcup SM, Gery I, Egwuagu CE (1998) Expression of ocular autoantigens in the mouse thymus. Curr Eye Res 17(8):788–792CrossRefPubMed
41.
Zurück zum Zitat Taylor AW, Streilein JW, Cousins SW (1992) Identification of alpha-melanocyte stimulating hormone as a potential immunosuppressive factor in aqueous humor. Curr Eye Res 11(12):1199–1206CrossRefPubMed Taylor AW, Streilein JW, Cousins SW (1992) Identification of alpha-melanocyte stimulating hormone as a potential immunosuppressive factor in aqueous humor. Curr Eye Res 11(12):1199–1206CrossRefPubMed
42.
Zurück zum Zitat Taylor AW, Yee DG (2003) Somatostatin is an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci 44(6):2644–2649CrossRefPubMed Taylor AW, Yee DG (2003) Somatostatin is an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci 44(6):2644–2649CrossRefPubMed
44.
Zurück zum Zitat Zhou R, Horai R, Silver PB, Mattapallil MJ, Zárate-Bladés CR, Chong WP, Chen J, Rigden RC, Villasmil R, Caspi RR (2012) the living eye “disarms” uncommitted autoreactive T cells by converting them to Foxp3(+) regulatory cells following local antigen recognition. J Immunol 188(4):1742. https://doi.org/10.4049/jimmunol.1102415 CrossRefPubMed Zhou R, Horai R, Silver PB, Mattapallil MJ, Zárate-Bladés CR, Chong WP, Chen J, Rigden RC, Villasmil R, Caspi RR (2012) the living eye “disarms” uncommitted autoreactive T cells by converting them to Foxp3(+) regulatory cells following local antigen recognition. J Immunol 188(4):1742. https://​doi.​org/​10.​4049/​jimmunol.​1102415 CrossRefPubMed
45.
Zurück zum Zitat Whitcup SM, DeBarge LR, Caspi RR, Harning R, Nussenblatt RB, Chan CC (1993) Monoclonal antibodies against ICAM-1 (CD54) and LFA-1 (CD11a/CD18) inhibit experimental autoimmune uveitis. Clin Immunol Immunopathol 67(2):143–150CrossRefPubMed Whitcup SM, DeBarge LR, Caspi RR, Harning R, Nussenblatt RB, Chan CC (1993) Monoclonal antibodies against ICAM-1 (CD54) and LFA-1 (CD11a/CD18) inhibit experimental autoimmune uveitis. Clin Immunol Immunopathol 67(2):143–150CrossRefPubMed
47.
Zurück zum Zitat Forrester JV, Huitinga I, Lumsden L, Dijkstra CD (1998) Marrow-derived activated macrophages are required during the effector phase of experimental autoimmune uveoretinitis in rats. Curr Eye Res 17(4):426–437CrossRefPubMed Forrester JV, Huitinga I, Lumsden L, Dijkstra CD (1998) Marrow-derived activated macrophages are required during the effector phase of experimental autoimmune uveoretinitis in rats. Curr Eye Res 17(4):426–437CrossRefPubMed
48.
Zurück zum Zitat Rosenbaum JT (2016) Extraarticular manifestations: uveitis. In: Inman R, Sieper J (eds) Textbook of axial spondylarthritis, 1st edn. Oxford University Press, Oxford, pp 145–148 Rosenbaum JT (2016) Extraarticular manifestations: uveitis. In: Inman R, Sieper J (eds) Textbook of axial spondylarthritis, 1st edn. Oxford University Press, Oxford, pp 145–148
58.
Zurück zum Zitat Adamus G, Manczak M, Machnicki M (2001) Expression of CC chemokines and their receptors in the eye in autoimmune anterior uveitis associated with EAE. Investigative ophthalmology & visual science 42(12):2894–2903 Adamus G, Manczak M, Machnicki M (2001) Expression of CC chemokines and their receptors in the eye in autoimmune anterior uveitis associated with EAE. Investigative ophthalmology & visual science 42(12):2894–2903
63.
Zurück zum Zitat Caspi RR, Chan CC, Grubbs BG, Silver PB, Wiggert B, Parsa CF, Bahmanyar S, Billiau A, Heremans H (1994) Endogenous systemic IFN-gamma has a protective role against ocular autoimmunity in mice. J Immunol (Baltimore, Md : 1950) 152(2):890–899 Issn: 0022–1767 Caspi RR, Chan CC, Grubbs BG, Silver PB, Wiggert B, Parsa CF, Bahmanyar S, Billiau A, Heremans H (1994) Endogenous systemic IFN-gamma has a protective role against ocular autoimmunity in mice. J Immunol (Baltimore, Md : 1950) 152(2):890–899 Issn: 0022–1767
64.
Zurück zum Zitat Hu MH, Zheng QF, Jia XZ, Li Y, Dong YC, Wang CY, Lin QY, Zhang FY, Zhao RB, Xu HW, Zhou JH, Yuan HP, Zhang WH, Ren H (2014) Neuroprotection effect of interleukin (IL)-17 secreted by reactive astrocytes is emerged from a high-level IL-17-containing environment during acute neuroinflammation. Clin Exp Immunol 175(2):268–284. https://doi.org/10.1111/cei.12219 CrossRefPubMedPubMedCentral Hu MH, Zheng QF, Jia XZ, Li Y, Dong YC, Wang CY, Lin QY, Zhang FY, Zhao RB, Xu HW, Zhou JH, Yuan HP, Zhang WH, Ren H (2014) Neuroprotection effect of interleukin (IL)-17 secreted by reactive astrocytes is emerged from a high-level IL-17-containing environment during acute neuroinflammation. Clin Exp Immunol 175(2):268–284. https://​doi.​org/​10.​1111/​cei.​12219 CrossRefPubMedPubMedCentral
71.
Zurück zum Zitat De Kozak Y, Thillaye Goldenberg B, Naud MC, Da Costa AV, Auriault C, Verwaerde C (2002) Inhibition of experimental autoimmune uveoretinitis by systemic and subconjunctival adenovirus-mediated transfer of the viral IL-10 gene. Clin Exp Immunol 130(2):212–223CrossRefPubMedPubMedCentral De Kozak Y, Thillaye Goldenberg B, Naud MC, Da Costa AV, Auriault C, Verwaerde C (2002) Inhibition of experimental autoimmune uveoretinitis by systemic and subconjunctival adenovirus-mediated transfer of the viral IL-10 gene. Clin Exp Immunol 130(2):212–223CrossRefPubMedPubMedCentral
73.
Zurück zum Zitat Agarwal RK, Horai R, Viley AM, Silver PB, Grajewski RS, Bo Su S, Yazdani AT, Zhu W, Kronenberg M, Murray PJ, Rutschman RL, Chan C-C, Caspi RR (2008) Abrogation of anti-retinal autoimmunity in IL-10 transgenic mice due to reduced T cell priming and inhibition of disease effector mechanisms. J Immunol 180(8):5423–5429. https://doi.org/10.4049/jimmunol.180.8.5423 CrossRefPubMed Agarwal RK, Horai R, Viley AM, Silver PB, Grajewski RS, Bo Su S, Yazdani AT, Zhu W, Kronenberg M, Murray PJ, Rutschman RL, Chan C-C, Caspi RR (2008) Abrogation of anti-retinal autoimmunity in IL-10 transgenic mice due to reduced T cell priming and inhibition of disease effector mechanisms. J Immunol 180(8):5423–5429. https://​doi.​org/​10.​4049/​jimmunol.​180.​8.​5423 CrossRefPubMed
74.
Zurück zum Zitat Streilein JW, Okamoto S, Hara Y, Kosiewicz M, Ksander B (1997) Blood-borne signals that induce anterior chamber-associated immune deviation after intracameral injection of antigen. Invest Ophthalmol Vis Sci 38(11):2245–2254PubMed Streilein JW, Okamoto S, Hara Y, Kosiewicz M, Ksander B (1997) Blood-borne signals that induce anterior chamber-associated immune deviation after intracameral injection of antigen. Invest Ophthalmol Vis Sci 38(11):2245–2254PubMed
76.
Zurück zum Zitat Namba K, Kitaichi N, Nishida T, Taylor AW (2002) Induction of regulatory T cells by the immunomodulating cytokines alpha-melanocyte-stimulating hormone and transforming growth factor-beta2. J Leukoc Biol 72(5):946–952PubMed Namba K, Kitaichi N, Nishida T, Taylor AW (2002) Induction of regulatory T cells by the immunomodulating cytokines alpha-melanocyte-stimulating hormone and transforming growth factor-beta2. J Leukoc Biol 72(5):946–952PubMed
83.
Zurück zum Zitat Jia X, Hu M, Wang C, Wang C, Zhang F, Han Q, Zhao R, Huang Q, Xu H, Yuan H, Ren H (2011) Coordinated gene expression of Th17- and Treg-associated molecules correlated with resolution of the monophasic experimental autoimmune uveitis. Mol Vis 17:1493–1507PubMedPubMedCentral Jia X, Hu M, Wang C, Wang C, Zhang F, Han Q, Zhao R, Huang Q, Xu H, Yuan H, Ren H (2011) Coordinated gene expression of Th17- and Treg-associated molecules correlated with resolution of the monophasic experimental autoimmune uveitis. Mol Vis 17:1493–1507PubMedPubMedCentral
86.
Zurück zum Zitat Crane IJ, Wallace CA, McKillop-Smith S, Forrester JV (2000) Control of chemokine production at the blood-retina barrier. Immunology 101(3):426–433CrossRefPubMedPubMedCentral Crane IJ, Wallace CA, McKillop-Smith S, Forrester JV (2000) Control of chemokine production at the blood-retina barrier. Immunology 101(3):426–433CrossRefPubMedPubMedCentral
97.
Zurück zum Zitat Ohnmacht C, Park J-H, Cording S, Wing JB, Atarashi K, Obata Y, Gaboriau-Routhiau V, Marques R, Dulauroy S, Fedoseeva M, Busslinger M, Cerf-Bensussan N, Boneca IG, Voehringer D, Hase K, Honda K, Sakaguchi S, Eberl G (2015) The microbiota regulates type 2 immunity through RORγt T cells. Science 349(6251):989–993. https://doi.org/10.1126/science.aac4263 CrossRefPubMed Ohnmacht C, Park J-H, Cording S, Wing JB, Atarashi K, Obata Y, Gaboriau-Routhiau V, Marques R, Dulauroy S, Fedoseeva M, Busslinger M, Cerf-Bensussan N, Boneca IG, Voehringer D, Hase K, Honda K, Sakaguchi S, Eberl G (2015) The microbiota regulates type 2 immunity through RORγt T cells. Science 349(6251):989–993. https://​doi.​org/​10.​1126/​science.​aac4263 CrossRefPubMed
Metadaten
Titel
Resolution of uveitis
verfasst von
Gerhild Wildner
Maria Diedrichs-Möhring
Publikationsdatum
07.10.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Seminars in Immunopathology / Ausgabe 6/2019
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-019-00758-z

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