A Review of the Various Roles and Participation Levels of B-Cells in Non-Infectious Uveitis

Wang

et al. 2021

Protein Cell

Self Cite

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs’ effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.

Section: Discussionmentioning

confidence: 99%

Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice

Wang

et al. 2021

Protein Cell

Self Cite

“…Although the function of B cells in EAU is less certain than that of T cells, increasing evidence supports their pathogenic functions in other autoimmune diseases, such as multiple sclerosis 9,32,33 . Thus, we re-clustered B cells and identified three B cell subtypes, including germinal center B cells (GC), naïve B cells, and PCs (Fig.…”

Section: Depleting B Cells Ameliorated Eaumentioning

confidence: 99%

“…Glucocorticoids, together with immunosuppressive drugs, cause various side effects and show limited efficacy 6 . Studies of the underlying pathological mechanisms are needed to develop specific, safe, and effective treatment regimens for uveitis.Abnormalities in various immune cells are critical contributors to autoimmune destruction in uveitis [7][8][9][10] . CD4 + T cells, especially regulatory (Treg) and effector (e.g., T helper (Th)−1 and Th17 cells) T cells, are considered pivotal in the pathogenesis of uveitis and its classic animal model, experimental autoimmune uveitis (EAU) 7,8,10 .…”

mentioning

confidence: 99%

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Multicellular immune dynamics implicate PIM1 as a potential therapeutic target for uveitis

Xie

et al. 2022

Nat Commun

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Uveitis is a severe autoimmune disease, and a common cause of blindness; however, its individual cellular dynamics and pathogenic mechanism remain poorly understood. Herein, by performing single-cell RNA sequencing (scRNA-seq) on experimental autoimmune uveitis (EAU), we identify disease-associated alterations in cell composition and transcriptional regulation as the disease progressed, as well as a disease-related molecule, PIM1. Inhibiting PIM1 reduces the Th17 cell proportion and increases the Treg cell proportion, likely due to regulation of PIM1 to the protein kinase B (AKT)/Forkhead box O1 (FOXO1) pathway. Moreover, inhibiting PIM1 reduces Th17 cell pathogenicity and reduces plasma cell differentiation. Importantly, the upregulation of PIM1 in CD4+ T cells and plasma cells is conserved in a human uveitis, Vogt-Koyanagi-Harada disease (VKH), and inhibition of PIM1 reduces CD4+ T and B cell expansion. Collectively, a dynamic immune cellular atlas during uveitis is developed and implicate that PIM1 may be a potential therapeutic target for VKH.

“…Rituximab (Rituxan, Genentech Inc) is an anti-CD-20 chimeric monoclonal antibody. There are many reports of rituximab in refractory NIU [186][187][188]. With regard to NIU, the efficacy of rituximab has been demonstrated in JIA, VKH and Behcet's disease-associated refractory uveitis [189][190][191][192].…”

Section: Cd-20 Inhibitormentioning

confidence: 99%

Pathogenesis and current therapies for non-infectious uveitis

Tao

et al. 2022

Clin Exp Med

Non-infectious uveitis (NIU) is a disorder with various etiologies and is characterized by eye inflammation, mainly affecting people of working age. An accurate diagnosis of NIU is crucial for appropriate therapy. The aim of therapy is to improve vision, relieve ocular inflammation, prevent relapse, and avoid treatment side effects. At present, corticosteroids are the mainstay of topical or systemic therapy. However, repeated injections are required for the treatment of chronic NIU. Recently, new drug delivery systems that may ensure intraocular delivery of therapeutic drug levels have been highlighted. Furthermore, with the development of immunosuppressants and biologics, specific therapies can be selected based on the needs of each patient. Immunosuppressants used in the treatment of NIU include calcineurin inhibitors and antimetabolites. However, systemic immunosuppressive therapy itself is associated with adverse effects due to the inhibition of immune function. In patients with refractory NIU or those who cannot tolerate corticosteroids and immunosuppressors, biologics have emerged as alternative treatments. Thus, to improve the prognosis of patients with NIU, NIU should be managed with different drugs according to the response to treatment and possible side effects.