Activation of immunosuppressive network in the aging process

Salminen, Antero

doi:10.1016/j.arr.2019.100998

Cited by 107 publications

(110 citation statements)

References 304 publications

(391 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The number of immunosuppressive macrophages, especially regulatory M2c subtype, increases in delayed inflammatory conditions and they secrete anti-inflammatory cytokines, e.g., IL-10 and TGF-β. Many other immune cells, i.e., T and B cells as well as dendritic, natural killer, and natural killer T cells, also involve regulatory, immunosuppressive phenotypes [132]. It is known that inflammatory mediators, e.g., those secreted by the ER-stressed nonimmune cells, are the major inducers of immunosuppressive phenotypes in infiltrated myeloid cells [111,112,133].…”

Section: Er Stress Augments the Immunosuppressive Phenotype Of Immunementioning

confidence: 99%

“…Since the immunosuppressive network functions in a cooperative manner, it seems that the increased presence of MDSCs and Tregs with aging promotes the polarization of other members to adopt the immunosuppressive phenotypes. We have recently reviewed the phenotypes of immune cells including in the immunosuppressive network and changes in their phenotypes during the aging process [132].…”

Section: Activation Of Immunosuppressive Network With Aging and Alzhementioning

confidence: 99%

See 1 more Smart Citation

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

2020

Self Cite

View full text Add to dashboard Cite

The endoplasmic reticulum (ER) contains stress sensors which recognize the accumulation of unfolded proteins within the lumen of ER, and subsequently these transducers stimulate the unfolded protein response (UPR). The ER sensors include the IRE1, PERK, and ATF6 transducers which activate the UPR in an attempt to restore the quality of protein folding and thus maintain cellular homeostasis. If there is excessive stress, UPR signaling generates alarmins, e.g., chemokines and cytokines, which activate not only tissue-resident immune cells but also recruit myeloid and lymphoid cells into the affected tissues. ER stress is a crucial inducer of inflammation in many pathological conditions. A chronic low-grade inflammation and cellular senescence have been associated with the aging process and many age-related diseases, such as Alzheimer's disease. Currently, it is known that immune cells can exhibit great plasticity, i.e., they are able to display both pro-inflammatory and anti-inflammatory phenotypes in a context-dependent manner. The microenvironment encountered in chronic inflammatory conditions triggers a compensatory immunosuppression which defends tissues from excessive inflammation. Recent studies have revealed that chronic ER stress augments the suppressive phenotypes of immune cells, e.g., in tumors and other inflammatory disorders. The activation of immunosuppressive network, including myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), has been involved in the aging process and Alzheimer's disease. We will examine in detail whether the ER stress-related changes found in aging tissues and Alzheimer's disease are associated with the activation of immunosuppressive network, as has been observed in tumors and many chronic inflammatory diseases.

show abstract

Section: Er Stress Augments the Immunosuppressive Phenotype Of Immunementioning

confidence: 99%

Section: Activation Of Immunosuppressive Network With Aging and Alzhementioning

confidence: 99%

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this way, there is an immunosuppressive network which is created as individuals are aging as coined by Salminen et al [184]. It seems that TGF-β, IL-10, and NO, secreted by MDSCs, are the major soluble mediators maintaining the functions of this age-related immunosuppressive network [185]. There is an abundant literature indicating that TGF-β signaling suppresses the functions of CD4 + [186] and CD8 + [187] T cells as well as DCs [188] and NK cells [189].…”

Section: Immunosuppressive Mechanismsmentioning

confidence: 99%

“…Together, the immunosuppressive network increase with aging may have several pathological consequences [184,185], but however, in the spirit of immunobiography, this can also be considered an adaptation to decrease the lifelong activation process of the innate immune system (innate immune memory) but unfortunately in the meantime downregulate adaptive immune activation.…”

Section: Immunosuppressive Mechanismsmentioning

confidence: 99%

Immunosenescence is both functional/adaptive and dysfunctional/maladaptive

et al. 2020

View full text Add to dashboard Cite

Alterations in the immune system with aging are considered to underlie many age-related diseases. However, many elderly individuals remain healthy until even a very advanced age. There is also an increase in numbers of centenarians and their apparent fitness. We should therefore change our unilaterally detrimental consideration of age-related immune changes. Recent data taking into consideration the immunobiography concept may allow for meaningful distinctions among various aging trajectories. This implies that the aging immune system has a homeodynamic characteristic balanced between adaptive and maladaptive aspects. The survival and health of an individual depends from the equilibrium of this balance. In this article, we highlight which parts of the aging of the immune system may be considered adaptive in contrast to those that may be maladaptive.

show abstract

“…Myeloid-derived suppressor cells (MDSCs) are a heterogeneous myeloid cell population characterized by immune regulatory properties (21,22). The differentiation and accumulation of MDSCs in human beings depends on pathological conditions such as cancer (23), infection (24), autoimmunity (25) and transplantation (26) but occurs during physiological processes such as aging (27) and pregnancy (28). MDSCs can be divided at least in three main subgroups according to the expression of selective surface markers: monocytic MDSC (M-MDSCs), that are characterized as CD11b + Ly6C + Ly6G − cells in mouse and CD11b + CD14 + CD15 − HLA-DR low/− CD124 + cells in human; polymorphonuclear-MDSC (PMN-MDSCs), that are identified as CD11b + Ly6C − Ly6G + cells in tumor-bearing mice and CD11b + CD14 − CD15 + HLA-DR low/− CD124 + cells in cancer patients (when the analysis is performed in low density mononuclear cell fraction); finally, the last MDSC subset is composed by "early immature" MDSCs (eMDSCs) defined as CD11b + Gr1 + CCR2 + Sca1 + CD31 + cells in mouse and Lin − CD11b + CD34 + CD33 + CD117 + HLA-DR low/− cells in human (8,21,29).…”

Section: Mdsc: a Tumor-induced Myeloid Cell Subsetmentioning

confidence: 99%

The Engagement Between MDSCs and Metastases: Partners in Crime

et al. 2020

View full text Add to dashboard Cite

Tumor metastases represent the major cause of cancer-related mortality, confirming the urgent need to identify key molecular pathways and cell-associated networks during the early phases of the metastatic process to develop new strategies to either prevent or control distal cancer spread. Several data revealed the ability of cancer cells to establish a favorable microenvironment, before their arrival in distant organs, by manipulating the cell composition and function of the new host tissue where cancer cells can survive and outgrow. This predetermined environment is termed "pre-metastatic niche" (pMN). pMN development requires that tumor-derived soluble factors, like cytokines, growth-factors and extracellular vesicles, genetically and epigenetically reprogram not only resident cells (i.e., fibroblasts) but also non-resident cells such as bone marrow-derived cells. Indeed, by promoting an "emergency" myelopoiesis, cancer cells switch the steady state production of blood cells toward the generation of pro-tumor circulating myeloid cells defined as myeloid-derived suppressor cells (MDSCs) able to sustain tumor growth and dissemination. MDSCs are a heterogeneous subset of myeloid cells with immunosuppressive properties that sustain metastatic process. In this review, we discuss current understandings of how MDSCs shape and promote metastatic dissemination acting in each fundamental steps of cancer progression from primary tumor to metastatic disease.

show abstract

Activation of immunosuppressive network in the aging process

Cited by 107 publications

References 304 publications

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

ER stress activates immunosuppressive network: implications for aging and Alzheimer’s disease

Immunosenescence is both functional/adaptive and dysfunctional/maladaptive

The Engagement Between MDSCs and Metastases: Partners in Crime

Contact Info

Product

Resources

About