Th17.1 lymphocytes: emerging players in the orchestra of immune-mediated inflammatory diseases

Misra, Durga Prasanna; Agarwal, Vikas

doi:10.1007/s10067-022-06202-2

Cited by 21 publications

(16 citation statements)

References 71 publications

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“…The term immune-mediated inflammatory diseases (IMIDs) encompasses several disease entities including definite, “classic” autoimmune disorders (ADs) (among others as systemic lupus erythematous/SLE/, rheumatoid arthritis/RA/); neurological disorders (such as multiple sclerosis); cutaneous inflammatory conditions (like psoriasis and atopic dermatitis); immune-mediated disorders with autoinflammatory characteristics such as the spondyloarthritis (SpA) disease spectrum, inflammatory bowel disease (IBD), asthma, graft-versus-host disease as well as other conditions in which the immune system is involved, but not the primary element of the pathogenesis (e.g., cancer or infectious disorders) [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Secretome: A Potential Therapeutic Option for Autoimmune and Immune-Mediated Inflammatory Diseases

Műzes

Sípos

2022

Cells

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Immune-mediated inflammatory diseases (IMIDs) encompass several entities such as “classic” autoimmune disorders or immune-mediated diseases with autoinflammatory characteristics. Adult stem cells including mesenchymal stem cells (MSCs) are by far the most commonly used type in clinical practice. However, due to the possible side effects of MSC-based treatments, there is an increase in interest in the MSC-secretome (containing large extracellular vesicles, microvesicles, and exosomes) as an alternative therapeutic option in IMIDs. A wide spectrum of MSC-secretome-related biological activities has been proven thus far including anti-inflammatory, anti-apoptotic, and immunomodulatory properties. In comparison with MSCs, the secretome is less immunogenic but exerts similar biological actions, so it can be considered as an ideal cell-free therapeutic alternative. Additionally, since the composition of the MSC-secretome can be engineered, for a future perspective, it could also be viewed as part of a potential delivery system within nanomedicine, allowing us to specifically target dysfunctional cells or tissues. Although many encouraging results from pre-clinical studies have recently been obtained that strongly support the application of the MSC-secretome in IMIDs, human studies with MSC-secretome administration are still in their infancy. This article reviews the immunomodulatory effects of the MSC-secretome in IMIDs and provides insight into the interpretation of its beneficial biological actions.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Secretome: A Potential Therapeutic Option for Autoimmune and Immune-Mediated Inflammatory Diseases

Műzes

Sípos

2022

Cells

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“…Generally, IFN-γ is secreted by Th1, Th17.1, CD8 + T cells, and NK cells in many physiological and pathological conditions. However, it is primarily produced by CD8 + T cells in the traumatic spinal cord, which might be because the number of CD8 + T cells infiltrated in the spinal cord was higher than other immune cells that produce IFN-γ after SCI [ 32 ]. Furthermore, IFN-γ is a key driver of the expression of PD-L1 that triggers T-cell exhaustion [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

IFN-γ-STAT1-mediated CD8+ T-cell-neural stem cell cross talk controls astrogliogenesis after spinal cord injury

Wang

Peng

et al. 2023

Inflamm Regener

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Background Spinal cord injury (SCI) causes nearly all patients to suffer from protracted disabilities. An emerging therapeutic strategy involving the recruitment of endogenous neural stem cells (NSCs) has been developed. However, endogenous NSCs in the adult spinal cord differentiate into mostly astrocytes after traumatic injury, forming glial scars, which is a major cause of regeneration failure in SCI. Thus, understanding which factors drive the activation and differentiation of endogenous NSCs after SCI is critical for developing therapeutic drugs. Methods The infiltration, state, and location of CD8+ T cells in spinal cord after traumatic injury were analyzed by flow cytometry and immunofluorescence (IF) staining. The Basso Mouse Scale (BMS) scores and rotarod testing were used for motor behavioral analysis. NSCs were co-cultured with CD8+ T cells. EdU assay was used to detect proliferative cells. Western blotting was used to analyze the expression levels of STAT1, p-STAT1, and p27. ChIP-seq and ChIP-qRT-PCR analyses were used to detect the downstream of STAT1. Nestin-CreERT2::Ai9 transgenic mice were used to genetic lineage tracing of Nestin+ NSCs after SCI in vivo. Results A prolonged increase of activated CD8+ T cells occurs in the injured spinal cords. The behavioral analysis demonstrated that the administration of an anti-CD8 antibody promotes the recovery of locomotor function. Then, we discovered that CD8+ T cells suppressed the proliferation of NSCs and promoted the differentiation of NSCs into astrocytes by the IFN-γ-STAT1 pathway in vitro. ChIP-seq and ChIP-qRT-PCR analysis revealed that STAT1 could directly bind to the promoters of astrocyte marker genes GFAP and Aldh1l1. Genetic lineage tracing of Nestin+ NSCs demonstrated that most NSCs differentiated into astrocytes following SCI. Depleting CD8+ T cells reduced the differentiation of NSCs into astrocytes and instead promoted the differentiation of NSCs into oligodendrocytes. Conclusion In conclusion, CD8+ T cells suppressed the proliferation of NSCs and promoted the differentiation of NSCs into astrocytes by the IFN-γ-STAT1-GFAP/Aldhl1l axis. Our study identifies INF-γ as a critical mediator of CD8+ T-cell-NSC cross talk and a potential node for therapeutic intervention in SCI.

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“…For example, heightened Th2 reactivity was found in cystic fibrosis patients that developed allergic bronchial‐pulmonary aspergillosis (ABPA) that could be reduced by vitamin D treatment 74 . It is now well established that Th17 lymphocytes associate with myriad immune‐mediated inflammatory diseases 75 . Th17 cells as important pro‐inflammatory cells, induce epithelial cells to produce antimicrobial peptides, chemokines, and granulocyte growth factors to promote neutrophil accumulation in airways 76 .…”

Section: Specific Immunity: Adaptive Immunitymentioning

confidence: 99%

Advances in immune response to pulmonary infection: Nonspecificity, specificity and memory

Xie

Cui³

2023

Chronic Diseases and Translational Medicine

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The lung immune response consists of various cells involved in both innate and adaptive immune processes. Innate immunity participates in immune resistance in a nonspecific manner, whereas adaptive immunity effectively eliminates pathogens through specific recognition. It was previously believed that adaptive immune memory plays a leading role during secondary infections; however, innate immunity is also involved in immune memory. Trained immunity refers to the long-term functional reprogramming of innate immune cells caused by the first infection, which alters the immune response during the second challenge. Tissue resilience limits the tissue damage caused by infection by controlling excessive inflammation and promoting tissue repair. In this review, we summarize the impact of host immunity on the pathophysiological processes of pulmonary infections and discuss the latest progress in this regard. In addition to the factors influencing pathogenic microorganisms, we emphasize the importance of the host response. K E Y W O R D S adaptive immunity, innate immunity, lung infection, trained immunity Highlights • Innate and adaptive immune responses constitute the basic mechanism of lung anti-infection immunity. • The classical adaptive immune response confers long-term and pathogenspecific protection. • Trained immunity enhances inflammatory and antimicrobial properties in a nonspecific manner.

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Th17.1 lymphocytes: emerging players in the orchestra of immune-mediated inflammatory diseases

Cited by 21 publications

References 71 publications

Mesenchymal Stem Cell-Derived Secretome: A Potential Therapeutic Option for Autoimmune and Immune-Mediated Inflammatory Diseases

Mesenchymal Stem Cell-Derived Secretome: A Potential Therapeutic Option for Autoimmune and Immune-Mediated Inflammatory Diseases

IFN-γ-STAT1-mediated CD8+ T-cell-neural stem cell cross talk controls astrogliogenesis after spinal cord injury

Advances in immune response to pulmonary infection: Nonspecificity, specificity and memory

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