The imbalance of tissue homeostasis in SpA is closely related to the abnormal regulation of this cytokine

*Only for medical professionals to read for reference.
The regulation of tissue homeostasis is a delicate task, and a little carelessness may lead to the occurrence and development of diseases
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 Spondyloarthritis (SpA) is a group of chronic inflammatory rheumatic diseases with specific pathophysiological, clinical, radiological and genetic characteristics, inflammatory low back pain with or without peripheral arthritis, plus certain characteristic extra-articular manifestations These are the unique symptoms and signs of this type of disease
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This type of diseases include: ankylosing spondylitis (AS), reactive arthritis (ReA), psoriatic arthritis (PsA), arthritis, inflammatory bowel disease (IBD) and the like
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SpA-related immunopathological mechanisms have always been the research content of scientific researchers, and their results will guide the further optimization of clinical treatment
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Interleukin-17A (IL-17A) is a cytokine discovered in recent years that plays a key role in the pathogenesis of SpA.
Many previous studies have explained the relationship between the occurrence and development of IL-17A and SpA from the perspective of genes and cell sources.
Let's change our perspective and look at the correlation between IL-17A and SpA from the maintenance of organizational homeostasis
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Human health is inseparable from the maintenance of tissue homeostasis.
Simply put, the structure and function of individual tissues are maintained in a relatively stable state
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This is a necessary condition for its normal functioning in the body and an important guarantee for maintaining the homeostasis of the entire internal environment.
If the tissue homeostasis is unbalanced, it may lead to the occurrence and development of diseases, and affect the treatment and prognosis of diseases[1-2]
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Therefore, the maintenance of tissue homeostasis is vital to human health
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The immune system may be more important than you think.
The human body has the ability to maintain homeostasis, so that the fluctuation of various physiological parameters is within an acceptable range
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At present, it is generally believed that the nervous system, endocrine system and immune system jointly regulate and maintain the body to maintain homeostasis
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Among them, the immune system is one of the most active systems in our body.
It plays a key role in the body's defense against foreign pathogens and is responsible for tissue repair and homeostasis [3]
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The immune system is a huge family consisting of a variety of immune cells, signaling molecules, tissues and organs
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When perceiving changes in the external environment such as infection, tissue pressure and injury, the immune system responds quickly, mobilizing different members, triggering a series of defensive responses, and bringing the body to a relative balance again
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These responses of the immune system are inflammatory reactions, and the ultimate goal is to restore the tissue to a steady state, which is beneficial to the health of the body [2]
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However, there is a degree in everything, and too much is not enough
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After the external stimulus is resolved, the inflammation needs to subside in time to rebuild the tissue homeostasis, otherwise the continuous inflammatory state may cause tissue damage and cause the body to enter a chronic pathological state [2]
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SpA is a group of chronic inflammatory diseases
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It is currently believed that SpA is a type of disease caused by immune disorders in the body under the interaction of various risk factors (such as mechanical stress, genetic susceptibility genes, microbial flora, etc.
) [4]
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In the continuous inflammation, the spine, sacroiliac joints and peripheral joints are invaded, the tissue homeostasis is unbalanced, and the structure is destroyed, causing the patient's dysfunction
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Taking AS as an example, AS is a disease with enthesitis and new bone formation as the key pathological features
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Under normal bone homeostasis, the inflammatory immune response at the injury site of the attachment point can drive tissue repair, but under pathological conditions, excessive activation of the immune system causes chronic inflammation and new bone formation, that is, excessive bone repair response, leading to the characteristic of AS disease The appearance of phenotype [5]
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So, how to grasp this "degree"? How does our body regulate the immune system to achieve tissue homeostasis? Tissue homeostasis is finely regulated by cytokines.
The maintenance of tissue homeostasis is regulated by the body's internal information
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As intercellular signaling molecules, cytokines can regulate a variety of signal transduction pathways, recruit immune cells and participate in the formation of the inflammatory microenvironment
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There has been quite a lot of literature describing the role of different cytokines, such as tumor necrosis factor-α (TNF-α), IL-23, IL-22, IL-17, etc.
in inflammation and tissue repair (Figure 1) [5 -8]
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Figure 1: Cytokines play a key role in spinal repair [5] According to their different functions in the inflammatory response, cytokines can be divided into pro-inflammatory cytokines and anti-inflammatory cytokines
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These two types of cells restrict and balance each other in the body and fine-tune the immune response to achieve the stability of the body's environment [9]
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Once the balance is broken, the self-regulatory mechanism becomes disordered, the body's homeostasis is disturbed, and the disease will follow
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IL-17A is an important pro-inflammatory cytokine that plays an important role in the protective immune response
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Studies have shown that increased levels of IL-17A contribute to the repair and healing of fractures and maintain bone tissue homeostasis [10-11]
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However, when overproduced, IL-17A can cause many diseases related to chronic inflammation, such as psoriasis and AS
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Research observations have found that in the serum and synovial fluid of patients with AS, the level of IL-17A is abnormally elevated [12-14], indicating that during the progression of the disease, the fine regulation of cytokines on tissue homeostasis is hindered
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At the AS attachment point, there are many immune cells resident here, such as type 3 innate lymphocytes (ILC3), natural killer (NK) cells, δγT cells, αβCD4+ and CD8+T cells
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Under the stimulation of IL-23, IL-6 and other cytokines, these immune cells are activated and further release other cytokines, such as IL-17A, TNF and IL-22, thereby enhancing inflammation signals and destroying tissue homeostasis
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In addition, IL-17A can also be produced through IL-23-independent pathways, and can exert pro-inflammatory effects independently of IL-23 (Figure 2) [5]
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Figure 2: Excessive activation of the immune system and excessive bone repair response during AS tissue injury [5] In AS, IL-17A not only destroys tissue homeostasis by amplifying inflammatory signals, but also participates in excessive tissue repair after inflammation
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It can regulate the activity and differentiation of osteoblasts through the JAK2/STAT3 signaling pathway, and promote subsequent new bone formation [12]
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In addition, mesenchymal stem cells (MSCs) have strong self-renewal ability and multi-directional differentiation potential, and are an important cell source for tissue repair.
After tissue is damaged, MSCs can differentiate into various types under the induction and stimulation of different cytokines.
Types of cells, rebuild tissue homeostasis
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IL-17A has a certain effect on the proliferation and differentiation of MSCs, and the increase of its expression level can promote the osteogenic differentiation of MSCs[5]
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In vitro studies and related experimental models have shown that, in the pathological immune response, the regulatory effect of IL-17A on tissue repair at the attachment point has exceeded the range of normal regulation, resulting in an imbalance of tissue homeostasis [15]
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It can be seen that cytokines play a key role in the maintenance of tissue homeostasis
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In the pathological process of AS, the increase of IL-17A expression level leads to abnormal regulation of tissue homeostasis by cytokines, causing excessive tissue repair, resulting in a series of structural damages such as new bone formation, bone fusion, and even osseous rigidity.

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Summary: The maintenance of tissue homeostasis is closely related to human health.
Many diseases arise from the imbalance of tissue homeostasis
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Under pathological conditions, the overactivity of cytokines may lead to excessive repair of tissues.
For example, the formation of new bone in AS is related to the excessive repair of bone tissue after inflammation
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IL-17A plays an important role in the maintenance of tissue homeostasis.
In AS disease, the increase in its expression level leads to increased inflammation and new bone formation.
Inhibition of IL-17A will help prevent excessive inflammation and bone tissue Over-repair, thereby restoring tissue homeostasis
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Experts comment on this article from the perspective of tissue homeostasis to explain the role of cytokine IL-17A in the pathological mechanism of SpA.
It is novel in concept.
The article first briefly introduces the important role of tissue homeostasis on human health, and then introduces the basic pathology of the immune system and SpA.
The mechanism and further elaborated the role of IL-17A in SpA inflammation and abnormal osteogenesis
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Starting from the overall view of the immune system, this article proposes the basic concepts of tissue homeostasis and its important role in the occurrence and development of diseases
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Highlighted the role of inflammatory cytokines in the inflammatory response and tissue repair, and pointed out that IL-17 is a key inflammatory factor of the AS inflammation axis, has a strong pro-inflammatory effect, and participates in the excessive repair of the tissue after inflammation, and promotes the abnormal formation of AS.
Bone
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It is fully proved that IL-17 is a key factor to break the tissue homeostasis of SpA patients
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The imbalance of tissue inflammation and repair may be the key basis for the formation of SpA abnormal new bone.
Therefore, in-depth study of the mechanism of IL-17 is of great significance for how to delay SpA radiological damage
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Expert profileProfessor Dongyi He, Deputy Dean of the Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Director, Chief Physician, and Doctoral Supervisor, Deputy Director, Rheumatism Branch of the Chinese Association of Integrative Medicine, Deputy Director, Rheumatism Branch of the Chinese Society of Chinese Medicine Member of the Standing Committee of the Chinese Medical Association Rheumatology Branch (seventh to tenth) Member of the Rheumatology Branch of the Shanghai Medical Association Chairman of the Rheumatology Branch of the Shanghai Society of Integrative Medicine State Council Special Allowance, Shanghai Leading Talents successively won honorary titles such as National Model Worker, National May 1st Labor Medal, Chinese Physician Award, etc.
Visiting Scholar of University of Texas in the United States.
In the past 10 years, he has undertaken more than 20 national and provincial scientific research projects as the first person in charge , (Presided over 3 general projects of the National Natural Science Foundation of China), received a total of more than 17 million yuan in scientific research funds and published more than 160 papers, with a total impact factor of 241.
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