The role of Syk in peripheral T cells

Park, Jeoung-Eun; Majumdar, Sirshendu; Brand, David; Rosloniec, Edward F.; Yi, Ae-Kyung; Stuart, J.; Kang, Andrew H.; Myers, Linda K.

doi:10.1016/j.clim.2018.04.007

Cited by 9 publications

(3 citation statements)

References 29 publications

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“…Studies have shown that SYK, JNK, and ERK play important regulatory roles in B cell receptor signaling pathways [18] . Syk, PI3K, JNK, and p38 can jointly affect T cell activation and participate in the T cell receptor signaling pathway [19][20][21] . Syk and JNK can participate in complement system-mediated phagocytosis, T cell activation, and inflammatory responses [22,23] .…”

Section: Discussionmentioning

confidence: 99%

The Involvement of the Fcεri Signaling Pathway in the Pathogenesis of Lacrimal Gland Benign Lymphoepithelial Lesions

Sun

et al. 2021

Preprint

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Objective: Benign lymphoepithelial lesion of lacrimal gland (LGBLEL) is a common orbital inflammatory disease with unknown pathogenesis. T his paper analyzed the role of the FcepsilonRI (FcεRI) signaling pathway in the pathogenesis of LGBLEL.Methods: Transcriptome sequencing and proteome sequencing were performed on LGBLEL and orbital CH diag nosed by histopathology in Beijing Tongren Hospital, Capital Medical University, between July 2010 and October 2013. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to jointly analyze the differentially expressed ge nes and proteins related to FcεRI signaling pathway. Four LGBLEL and three orbital CH diagnosed by histopathology in Beijing Tongren Hospital, Capital Medical University, between October 2018 and August 2019 were randomly selected as the experimental group and the control group, respectively. RT PCR, immunohistochemical staining, and western blotting were used to verify the genes and proteins related to the FcεRI signaling pathway.Results: Combined transcriptome and proteome analysis showed that the FcεRI signaling pathway was up regulated in LGBLEL (P=0.0040), and that the important proteins such as SYK, p38, JNK, PI3K, and ERK were highly expressed in LGBLEL tissues. RT PCR results showed that the mRNA expression levels of SYK, p38, JNK, PI3K, and ERK wer e significantly increased in the LGBLEL group (P=0.0066, P=0.0002, P=0.0003, P<0.0001, P<0.0001, respectively). Immunohistochemical staining results showed that the protein expression levels of SYK, p38, JNK, PI3K, and ERK in LGBLEL tissues were significan tly higher than in orbital CH. Western Blotting showed that the protein contents of p SYK, p p38, p JNK, p PI3K, and p ERK were significantly higher than in orbital CH (P=0.0169, P=0.0074, P=0.0046, P=0.0157, P=0.0156, respectively). Conclusion: The genes and proteins related to the FcεRI signaling pathway are up regulated in LGBLEL, indicating that the FcεRI signaling pathway participates in the pathogenesis of LGBLEL.

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Section: Discussionmentioning

confidence: 99%

The Involvement of the Fcεri Signaling Pathway in the Pathogenesis of Lacrimal Gland Benign Lymphoepithelial Lesions

Sun

et al. 2021

Preprint

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“…Leukocyte-associated immunoglobulin receptors 1 and 2 (LAIR-1 and LAIR-2, respectively) are inhibitory immune receptors for collagens that are expressed broadly across the immune compartment (103,104). LAIR-1 engagement by collagen or the complement component C1q induces inhibitory T cell signalling (105), and in collagen-induced arthritis, administration of anti-LAIR-1 antibodies significantly attenuated disease (106, 107). In RA, T cell expression of LAIR-1 is reduced compared to healthy and osteoarthritis controls and elevated on ST monocytes and macrophages (108).…”

Section: Other Pathwaysmentioning

confidence: 99%

Immune checkpoints in rheumatoid arthritis: progress and promise

Small,

Lowe,

Wechalekar

2023

Front. Immunol.

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Rheumatoid arthritis (RA) is one of the most prevalent autoimmune inflammatory conditions, and while the mechanisms driving pathogenesis are yet to be completely elucidated, self-reactive T cells and immune checkpoint pathways have a clear role. In this review, we provide an overview of the importance of checkpoint pathways in the T cell response and describe the involvement of these in RA development and progression. We discuss the relationship between immune checkpoint therapy in cancer and autoimmune adverse events, draw parallels with the involvement of immune checkpoints in RA pathobiology, summarise emerging research into some of the lesser-known pathways, and the potential of targeting checkpoint-related pathways in future treatment approaches to RA management.

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“…Activation of LAIR-1 in vitro potently inhibits diverse immune cells such as T cells, NK cells (Jansen et al, 2007;Maasho et al, 2005;Meyaard et al, 1997;Park et al, 2020), B cells (Merlo et al, 2005) plasmacytoid dendritic cells (pDC) (Bonaccorsi et al, 2010;Son et al, 2012) and monocytes (Carvalheiro et al, 2020;Keerthivasan et al, 2021;Son and Diamond, 2015). LAIR-1 inhibitory function can be regulated at the membrane expression level and by the natural soluble agonists soluble-LAIR-1 (sLAIR-1), a shed form of LAIR-1, and LAIR-2.…”

Section: Introductionmentioning

confidence: 99%

Impaired LAIR-1-mediated immune control due to collagen degradation in fibrosis

Carvalheiro

Marut

Ramos

et al. 2021

Preprint

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Tissue repair is disturbed in fibrotic diseases like systemic sclerosis (SSc), where the deposition of large amounts of extracellular matrix components such as collagen interferes with organ function. LAIR-1 is an inhibitory collagen receptor highly expressed on tissue immune cells. We questioned whether in SSc, impaired LAIR-1-collagen interaction is contributing to the ongoing inflammation and fibrosis. We found that SSc patients do not have an intrinsic defect in LAIR-1 expression or function. Instead, fibroblasts from SSc patients deposit disorganized collagen products in vitro, which are dysfunctional LAIR-1 ligands. This can be mimicked in healthy fibroblast stimulated by soluble factors that drive inflammation and fibrosis in SSc and is dependent of matrix metalloproteinases and platelet-derived growth factor receptor signaling. In support of a non-redundant role of LAIR-1 in the control of fibrosis, we found that LAIR-1-deficient mice have increased skin fibrosis in the bleomycin mouse model for SSc. Thus, LAIR-1 represents an essential control mechanism for tissue repair. In fibrotic disease, excessive collagen degradation may lead to a disturbed feedback loop. The presence of functional LAIR-1 in patients provides a therapeutic opportunity to reactivate this intrinsic negative feedback mechanism in fibrotic diseases.

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The role of Syk in peripheral T cells

Cited by 9 publications

References 29 publications

The Involvement of the Fcεri Signaling Pathway in the Pathogenesis of Lacrimal Gland Benign Lymphoepithelial Lesions

The Involvement of the Fcεri Signaling Pathway in the Pathogenesis of Lacrimal Gland Benign Lymphoepithelial Lesions

Immune checkpoints in rheumatoid arthritis: progress and promise

Impaired LAIR-1-mediated immune control due to collagen degradation in fibrosis

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