scholarly journals The Innate Immune Cell Profile of the Cornea Predicts the Onset of Ocular Surface Inflammatory Disorders

2019 ◽  
Vol 8 (12) ◽  
pp. 2110 ◽  
Author(s):  
Amaya Pérez del Palomar ◽  
Alberto Montolío ◽  
José Cegoñino ◽  
Sandeep Kumar Dhanda ◽  
Chit Tong Lio ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune System ◽  
Sjögren’S Syndrome ◽  
Immune Cells ◽  
Ocular Surface ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Inflammatory Disorder ◽  
Sjögren‘S Syndrome

Ocular surface inflammatory disorder (OSID) is a spectrum of disorders that have features of several etiologies whilst displaying similar phenotypic signs of ocular inflammation. They are complicated disorders with underlying mechanisms related to several autoimmune disorders, such as rheumatoid arthritis (RA), Sjögren’s syndrome, and systemic lupus erythematosus (SLE). Current literature shows the involvement of both innate and adaptive arms of the immune system in ocular surface inflammation. The ocular surface contains distinct components of the immune system in the conjunctiva and the cornea. The normal conjunctiva epithelium and sub-epithelial stroma contains resident immune cells, such as T cells, B cells (adaptive), dendritic cells, and macrophages (innate). The relative sterile environment of the cornea is achieved by the tolerogenic properties of dendritic cells in the conjunctiva, the presence of regulatory lymphocytes, and the existence of soluble immunosuppressive factors, such as the transforming growth factor (TGF)-β and macrophage migration inhibitory factors. With the presence of both innate and adaptive immune system components, it is intriguing to investigate the most important leukocyte population in the ocular surface, which is involved in immune surveillance. Our meta-analysis investigates into this with a focus on both infectious (contact lens wear, corneal graft rejection, Cytomegalovirus, keratitis, scleritis, ocular surgery) and non-infectious (dry eye disease, glaucoma, graft-vs-host disease, Sjögren’s syndrome) situations. We have found the predominance of dendritic cells in ocular surface diseases, along with the Th-related cytokines. Our goal is to improve the knowledge of immune cells in OSID and to open new dimensions in the field. The purpose of this study is not to limit ourselves in the ocular system, but to investigate the importance of dendritic cells in the disorders of other mucosal organs (e.g., lungs, gut, uterus). Holistically, we want to investigate if this is a common trend in the initiation of any disease related to the mucosal organs and find a unified therapeutic approach. In addition, we want to show the power of computational approaches to foster a collaboration between computational and biological science.

scholarly journals POS0109 IDENTIFICATION OF PRIMARY SJOGREN’S SYNDROME SUBTYPES BY MACHINE LEARNING

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 265.2-266
Author(s):  
M. T. Qiu ◽  
S. X. Zhang ◽  
J. Qiao ◽  
J. Q. Zhang ◽  
S. Song ◽  
...  
Keyword(s):  
Machine Learning ◽  
Sjögren’S Syndrome ◽  
Immune Cells ◽  
Immune Cell ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren Syndrome ◽  
Sjogren Syndrome ◽  
Sjögren‘S Syndrome

Background:Sjogren’s syndrome(pSS) is a chronic, progressive, and systematic autoimmune disease characterized by lymphocytic infiltration of exocrine glands 1 2. Sicca symptoms and abnormal fatigue are the main clinical presentation, but those symptoms are non-specific to patients, which lead to delayed diagnosis 1 3. The heterogeneous of clinical manifestation raise challenges regarding diagnosis and therapy in pSS, thus it’s necessary for us to sub-classify pSS.Objectives:To explore new biomarkers for diagnosis and subtypes of pSS based on Machine Learning Primary.Methods:All microarray raw datas (CEL files) were screened and downloaded from Gene Expression Omnibus (GEO). Meta-analysis to identify the consistent DEGs by MetaOmics. Weighted gene co-expression network analysis (WGCNA) was used to the modules related to SS for further analysis. Subclasses were computed using a consensus Non-negative Matrix Factorization (NMF) clustering method. Immune cell infiltration was used to evaluate the expression of immune cells and obtain various immune cell proportions from samples. P value < 0.05 were considered statistically significant. All the analyses were conducted under R environment (version 4.03).Results:A total of 3715 consistent DEGs were identified from the four datasets, including 1748 up-regulated and 1967 down-regulated genes. Tour meaningful modules, including yellow, turquoise, grey60 and bule, were identified (Figure 1A,1B). And 183 overlapping gene were screened from the DEGs and the Hub genes in the four modles for further analysis. We final divided pSS patients into three subtypes, of which yellow and turquoise in Sub1, grey60 in Sub2 and blue in Sub3. Sub1 and Sub3 were related to cell metabolism, while Sub2 had connection with virus infection (Figure 1C,1D). Infiltrated immune cells were also different among these three types (Figure 1E,1F).Conclusion:Patients with pSS could be classified into 3 subtypes, this classification might help for assessing prognosis and guiding precise treatment.References:[1]Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, et al. Primary Sjogren syndrome. BMJ (Clinical research ed) 2012;344:e3821. doi: 10.1136/bmj.e3821 [published Online First: 2012/06/16].[2]Brito-Zeron P, Baldini C, Bootsma H, et al. Sjogren syndrome. Nat Rev Dis Primers 2016;2:16047. doi: 10.1038/nrdp.2016.47 [published Online First: 2016/07/08].[3]Segal B, Bowman SJ, Fox PC, et al. Primary Sjogren’s Syndrome: health experiences and predictors of health quality among patients in the United States. Health Qual Life Outcomes 2009;7:46. doi: 10.1186/1477-7525-7-46 [published Online First: 2009/05/29].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

Levels of plasmacytoid dendritic cells and type-2 myeloid dendritic cells are reduced in peripheral blood of patients with primary Sjögren's syndrome

2009 ◽  
Vol 69 (6) ◽  
pp. 1235-1238 ◽  
Author(s):  
Petra Vogelsang ◽  
Johan G Brun ◽  
Gunnvor Øijordsbakken ◽  
Kathrine Skarstein ◽  
Roland Jonsson ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Sjögren’S Syndrome ◽  
Peripheral Blood ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Healthy Controls ◽  
Myeloid Dendritic Cells ◽  
Antigen Presenting ◽  
Sjögren‘S Syndrome

ObjectiveSjögren's syndrome (SS) is a lymphoproliferative autoimmune disease, characterised by dryness of the mouth and eyes. Dendritic cells (DC) are potent antigen-presenting cells crucial for initiating and maintaining primary immune responses. This study quantified interferon-producing plasmacytoid DC (pDC) and two myeloid DC subsets (mDC1 and mDC2) in peripheral blood (PB) from primary SS (pSS) patients and healthy controls.MethodsBlood samples from 31 pSS patients and 28 gender and age-matched healthy controls were analysed by flow cytometry using the Miltenyi Blood DC enumeration kit. The presence of pDC in salivary glands (SG) from pSS patients was analysed by immunohistochemistry.ResultsPatients with pSS had significantly less pDC and mDC2 in PB compared with healthy controls. Moreover, pDC are present in SG from patients with pSS.ConclusionPatients with pSS have alterations among DC populations in PB, and pDC are present in the SG, suggesting a potential role of these cells in SS.

scholarly journals DENDRITIC CELLS IN PRIMARY SJOGREN'S SYNDROME

2019 ◽  
Author(s):  
WANESSA SIQUEIRA CAVALCANTE ◽  
SHEYLA BATISTA BOLOGNA LOPES ◽  
SILVIA VANESSA LOURENCO ◽  
LUIZ FERNANDO FERRAZ DA SILVA ◽  
MARCELLO MENTA SIMONSEN NICO
Keyword(s):  
Dendritic Cells ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Primary Sjögren’S Syndrome ◽  
Primary Sjogren’S Syndrome ◽  
Primary Sjögren's Syndrome ◽  
Sjögren‘S Syndrome

scholarly journals TLR7 Signaling Drives the Development of Sjögren’s Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Yawen Wang ◽  
Annie Roussel-Queval ◽  
Lionel Chasson ◽  
Noël Hanna Kazazian ◽  
Laetitia Marcadet ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Autoimmune Disease ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Autoantibody Production ◽  
Deficient Mice ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a chronic systemic autoimmune disease that affects predominately salivary and lacrimal glands. SS can occur alone or in combination with another autoimmune disease like systemic lupus erythematosus (SLE). Here we report that TLR7 signaling drives the development of SS since TLR8-deficient (TLR8ko) mice that develop lupus due to increased TLR7 signaling by dendritic cells, also develop an age-dependent secondary pathology similar to associated SS. The SS phenotype in TLR8ko mice is manifested by sialadenitis, increased anti-SSA and anti-SSB autoantibody production, immune complex deposition and increased cytokine production in salivary glands, as well as lung inflammation. Moreover, ectopic lymphoid structures characterized by B/T aggregates, formation of high endothelial venules and the presence of dendritic cells are formed in the salivary glands of TLR8ko mice. Interestingly, all these phenotypes are abrogated in double TLR7/8-deficient mice, suggesting that the SS phenotype in TLR8-deficient mice is TLR7-dependent. In addition, evaluation of TLR7 and inflammatory markers in the salivary glands of primary SS patients revealed significantly increased TLR7 expression levels compared to healthy individuals, that were positively correlated to TNF, LT-α, CXCL13 and CXCR5 expression. These findings establish an important role of TLR7 signaling for local and systemic SS disease manifestations, and inhibition of such will likely have therapeutic value.

Measuring the Lacunar Sulci as a New Indicator of Shrinkage of the Ocular Surface

2001 ◽  
Vol 11 (3) ◽  
pp. 227-232 ◽  
Author(s):  
J. Murube ◽  
L. Chenzhuo ◽  
E. Murube ◽  
L. Rivas ◽  
O. Shalaby
Keyword(s):  
Sjögren’S Syndrome ◽  
Ocular Surface ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Vanishing Point ◽  
Cicatricial Pemphigoid ◽  
Ocular Cicatricial Pemphigoid ◽  
Healthy Persons ◽  
Sjögren‘S Syndrome

Purpose To present a new indicator that measures the sulci of the lacrimal lake of the eye according to the degrees of ocular abduction at which they vanish. This new approach will help determine the severity and progression of mucosal retraction in ocular surface diseases. Methods A total of 181 eyes of 94 healthy persons, 130 eyes of 65 patients with Sjögren's syndrome, and 30 eyes of 15 patients with ocular pemphigoid were examined using the slit lamp. We recorded the vanishing point of the three main lacunar sulci (plico-bulbar, plico-caruncular and dermo-caruncular) while abducting. Results In healthy persons, the average vanishing points for the first and second lacunar sulci were respectively, 53.2° ± 12.3 and 54.5° ± 9.8. In patients with Sjögren's syndrome, 49.53° ± 10.81 and 53.17° ± 7.28 and in patients with incipient ocular cicatricial pemphigoid, 42.69° ± 14.33 and 44.46° ± 16.85. Statistical significance was p < 0.005. Conclusions The lacunar sulci are shallower and vanish sooner in ocular cicatricial pemphigoid and Sjögren syndrome than in normals. Investigating the vanishing point of the lacunar sulci while abducting is useful for grading the shrinkage of the conjunctiva, caruncle and medial canthus.

scholarly journals Sjögren’s Syndrome-Like Ocular Surface Disease in Thrombospondin-1 Deficient Mice

2009 ◽  
Vol 175 (3) ◽  
pp. 1136-1147 ◽  
Author(s):  
Bruce Turpie ◽  
Takeru Yoshimura ◽  
Abha Gulati ◽  
Jose David Rios ◽  
Darlene A. Dartt ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
Ocular Surface ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Ocular Surface Disease ◽  
Thrombospondin 1 ◽  
Deficient Mice ◽  
Sjögren‘S Syndrome

scholarly journals Modulation of Conjunctival Goblet Cell Function by Inflammatory Cytokines

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
L. Contreras-Ruiz ◽  
A. Ghosh-Mitra ◽  
M. A. Shatos ◽  
D. A. Dartt ◽  
S. Masli
Keyword(s):  
Sjögren’S Syndrome ◽  
Inflammatory Cytokines ◽  
Goblet Cell ◽  
Ocular Surface ◽  
Cell Function ◽  
Sjögren's Syndrome ◽  
Goblet Cells ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

Ocular surface inflammation associated with Sjögren’s syndrome is characterized by a loss of secretory function and alteration in numbers of mucin secreting goblet cells. Such changes are a prominent feature of ocular surface inflammatory diseases and are attributed to inflammation; however, the exact effect of the inflammatory cytokines on conjunctival goblet cell function remains largely unknown. In this study, we developed a primary culture of mouse goblet cells from conjunctival tissue and evaluated the effects on their function by inflammatory cytokines detected in the conjunctiva of mouse model of Sjögren’s syndrome (Thrombospondin-1 deficient mice). We found that apoptosis of goblet cells was primarily induced by TNF-αand IFN-γ. These two cytokines also inhibited mucin secretion by goblet cells in response to cholinergic stimulation, whereas IL-6 enhanced such secretion. No changes in secretory response were detected in the presence of IL-13 or IL-17. Goblet cells proliferated to varying degrees in response to all the tested cytokines with the greatest response to IL-13 followed by IL-6. Our results therefore reveal that inflammatory cytokines expressed in the conjunctiva during an ocular surface disease directly disrupt conjunctival goblet cell functions, compromising the protective function of tears, thereby contributing to ocular surface damage.

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