8 pictures summarize the pathogenesis of RA, worthy of collection

✦ The role of genetic factors in RA

https://doi.

In genetically susceptible individuals, host and environmental factors can lead to the activation of pathogenic T cells and the ensuing cascade of inflammatory responses

✦RA-related epigenetic modification and drug intervention

DOI: 10.

✦The role of innate immune cells in the pathogenesis of RA

https://doi.

Monocytes, macrophages, dendritic cells, neutrophils, natural killer cells and innate lymphocytes play key roles in the early stages and progression of rheumatoid arthritis

✦Innate immune signaling in RA

https://doi.

Upon ligand binding, Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs) activate a series of intracellular signaling events, leading to the activation of various transcription factors, ultimately inducing gene transcription and secretion of various Pro-inflammatory cytokines (eg TNF, IL-6, type I interferon (IFN)) and growth factors (eg GM-CSF)

Caspase-1 exists in the cytoplasm as an inactive zymogen and requires a molecular platform, the inflammasome, for activation

✦The effect of altered miRNA expression in various cells of RA patients

https://doi.

RASFs: rheumatoid arthritis synovial fibroblasts, PBMCs: peripheral blood mononuclear cells, Th17: T-helper 17 cells, Tregs: T-regulatory cells, MMPs: matrix metalloproteinases, NF-κB: nuclear factor κβ, TLR: toll-like receptor, JAK/STAT: Janus kinase/activator of signaling and transcriptional proteins

✦T cell activation in the pathogenesis of RA

https://doi.

T cell receptors (TCRs) bind and recognize components of the major histocompatibility complex (MHC) and peptides to initiate signaling 1

✦The role of cytokines in the pathogenesis of RA

https://doi.

Cytokines are important mediators of local intercellular communication

✦RA's ​​Bone Destruction Model

https://doi.

The accumulation of cytokines, osteoclasts, interleukins, and macrophages can lead to pannus formation, which can further lead to cartilage destruction in rheumatoid arthritis patients

✦ The role of genetic factors in RA

https://doi.

In genetically susceptible individuals, host and environmental factors can lead to the activation of pathogenic T cells and the ensuing cascade of inflammatory responses
.
Cytokines are involved in coordinating immune responses and the recruitment and activation of effector cells, which can lead not only to inflammation but also to local tissue damage in RA joints
.
APC, antigen presenting cell
.

✦RA-related epigenetic modification and drug intervention

DOI: 10.
3389/fimmu.
2022.
859400

✦The role of innate immune cells in the pathogenesis of RA

https://doi.
org/10.
1016/j.
bj.
2020.
06.
010

Monocytes, macrophages, dendritic cells, neutrophils, natural killer cells and innate lymphocytes play key roles in the early stages and progression of rheumatoid arthritis
.

✦Innate immune signaling in RA

https://doi.
org/10.
1016/j.
bj.
2020.
06.
010

Upon ligand binding, Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs) activate a series of intracellular signaling events, leading to the activation of various transcription factors, ultimately inducing gene transcription and secretion of various Pro-inflammatory cytokines (eg TNF, IL-6, type I interferon (IFN)) and growth factors (eg GM-CSF)
.
However, one of the cytokines failed to secrete IL-1β because it was not processed by caspase-1 (caspase-1)
.

Caspase-1 exists in the cytoplasm as an inactive zymogen and requires a molecular platform, the inflammasome, for activation
.
So when a danger signal is sensed, it gets activated
.
At this time, Caspase-1 also cleaves gasdermin D (GSDMD) into two fragments (N- and C-terminal)
.
The N-terminal fragment of GSDMD then oligomerizes and forms a pore in the plasma membrane, releasing active IL-1β and other cellular components
.
All these cytokines then act locally or systemically to promote an inflammatory state in the synovium and activate/attract various immune cells that initiate and contribute to RA pathogenesis
.

✦The effect of altered miRNA expression in various cells of RA patients

https://doi.
org/10.
1016/j.
autrev.
2019.
102391

RASFs: rheumatoid arthritis synovial fibroblasts, PBMCs: peripheral blood mononuclear cells, Th17: T-helper 17 cells, Tregs: T-regulatory cells, MMPs: matrix metalloproteinases, NF-κB: nuclear factor κβ, TLR: toll-like receptor, JAK/STAT: Janus kinase/activator of signaling and transcriptional proteins

✦T cell activation in the pathogenesis of RA

https://doi.
org/10.
1016/j.
mpmed.
2021.
12.
001

T cell receptors (TCRs) bind and recognize components of the major histocompatibility complex (MHC) and peptides to initiate signaling 1
.
There are many different variants of T cell receptors and MHC molecules
.
However, this was not enough to activate T cells
.
Activation requires the participation of costimulatory pathways
.
CD80/86:CD28 is the most typical costimulatory pathway
.
CD28 is constitutively expressed on T cells and binds to CD80/86
.
CD80/86:CD28 promotes T cell activation, proliferation, survival and cytokine production
.

✦The role of cytokines in the pathogenesis of RA

https://doi.
org/10.
1016/j.
mpmed.
2021.
12.
001

Cytokines are important mediators of local intercellular communication
.
They play a key role in integrating responses to various stimuli during the inflammatory process, and an imbalance of pro- and anti-inflammatory cytokines is thought to contribute to RA; pro-inflammatory cytokine production is upregulated, while transforming growth factor (TGF) )-β and other anti-inflammatory cytokines are not up-regulated enough to achieve equilibrium
.

✦RA's ​​Bone Destruction Model

https://doi.
org/10.
1016/j.
sjbs.
2021.
09.
014

The accumulation of cytokines, osteoclasts, interleukins, and macrophages can lead to pannus formation, which can further lead to cartilage destruction in rheumatoid arthritis patients
.