Mesenchymal stromal cells (MSCs) as a therapeutic agent of inflammatory disease and infectious COVID-19 virus: live or dead mesenchymal?

The COVID-19 infection is a worldwide disease that causes numerous immune-inflammatory disorders, tissue damage, and lung dysfunction. COVID-19 vaccines, including those from Pfizer, AstraZeneca, and Sinopharm, are available globally as effective interventions for combating the disease. The severity of COVID-19 can be most effectively reduced by mesenchymal stromal cells (MSCs) because they possess anti-inflammatory activity and can reverse lung dysfunction. MSCs can be harvested from various sources, such as adipose tissue, bone marrow, peripheral blood, inner organs, and neonatal tissues. The regulation of inflammatory cytokines is crucial in inhibiting inflammatory diseases and promoting the presence of anti-inflammatory cytokines for infectious diseases. MSCs have been employed as therapeutic agents for tissue damage, diabetes, autoimmune diseases, and COVID-19 patients. Our research aimed to determine whether live or dead MSCs are more suitable for the treatment of COVID-19 patients. Our findings concluded that dead MSCs, when directly administered to the patient, offer advantages over viable MSCs due to their extended presence and higher levels of immune regulation, such as T-reg, B-reg, and IL-10, compared to live MSCs. Additionally, dead and apoptotic MSCs are likely to be more readily captured by monocytes and macrophages, prolonging their presence compared to live MSCs.

A glance on the role of IL-35 in systemic lupus erythematosus (SLE).

It is well known that systemic lupus erythematosus (SLE) is an auto-inflammatory disease that is characterized by chronic and widespread inflammation. The exact pathogenesis of SLE is still a matter of debate. However, it has been suggested that the binding of autoantibodies to autoantigens forms immune complexes (ICs), activators of the immune response, in SLE patients. Ultimately, all of these responses lead to an imbalance between anti-inflammatory and pro-inflammatory cytokines, resulting in cumulative inflammation. IL-35, the newest member of the IL-12 family, is an immunosuppressive and anti-inflammatory cytokine secreted mainly by regulatory cells. Structurally, IL-35 is a heterodimeric cytokine, composed of Epstein-Barr virus-induced gene 3 (EBI3) and p35. IL-35 appears to hold therapeutic and diagnostic potential in cancer and autoimmune diseases. In this review, we summarized the most recent associations between IL and 35 and SLE. Unfortunately, the comparative review of IL-35 in SLE indicates many differences and contradictions, which make it difficult to generalize the use of IL-35 in the treatment of SLE. With the available information, it is not possible to talk about targeting this cytokine for the lupus treatment. So, further studies would be needed to establish the clear and exact levels of this cytokine and its related receptors in people with lupus to provide IL-35 as a preferential therapeutic or diagnostic candidate in SLE management.

A better understanding of the role of the CTLA-CD80/86 axis in the treatment of autoimmune diseases.

Autoimmune diseases are diseases in which the regulatory mechanisms of the immune response are disturbed. As a result, the body loses self-tolerance. Since one of the main regulatory mechanisms of the immune response is the CTLA4-CD80/86 axis, this hypothesis suggests that autoimmune diseases potentially share a similar molecular basis of pathogenesis. Hence, investigating the CTLA4-CD80/86 axis may be helpful in finding an appropriate treatment strategy. Therefore, this study aims to investigate the molecular basis of the CTLA4-CD80/86 axis in the regulation of the immune response, and then its role in developing some autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. As well, the main therapeutic strategies affecting the CTLA4-CD80/86 axis have been summarized to highlight the importance of this axis in management of autoimmune diseases.

Regulatory NK cells in autoimmune disease.

NK cells are defined as the major components of the immunological network which exerts defense against tumors and viral infections as well as regulation of innate and adaptive immunity, shaped through interaction with other cells like T cells. According to the surface markers, NK cells can be divided into CD56dim NK and CD56bright NK subsets. CD56bright NK cells usually are known as regulatory NK cells. Once the immune system loses its self-tolerance, autoimmune diseases develop. NK cells and their subsets can be altered during autoimmune diseases, indicative of their prominent regulatory roles and even pathological and protective functions in autoimmune disorders. In this regard, activation of CD56bright NK cells can suppress activated autologous CD4+ T cells and subsequently prevent the initiation of autoimmunity. In this review article, we summarize the roles of regulatory NK cells in autoimmune disease occurrence which needs more research to uncover their exact related mechanism. It seems that targeting NK cells can be a promising therapeutic platform against autoimmune diseases.

Implications of IL-21 in solid tumor therapy.

Cancer, the most deadly disease, is known as a recent dilemma worldwide. Presently different treatments are used for curing cancers, especially solid cancers. Because of the immune-enhancing functions of cytokine, IL-21 as a cytokine may have new possibilities to manipulate the immune system in disease conditions, as it stimulates NK and CTL functions and drives IgG antibody production. Indeed, IL-21 has been revealed to elicit antitumor-immune responses in several tumor models. Combining IL-21 with other agents, which target tumor cells, immune-regulatory circuits, or other immune-enhancing molecules enhances this activity. The exciting breakthrough in the results obtained in pre-clinical situations has led to the early outset of present developing clinical trials in cancer patients. In the paper, we have reviewed the function of IL-21 in solid tumor immunotherapy.

Impacts of Porphyromonas gingivalis periodontitis on rheumatoid arthritis autoimmunity.

In RA patients' synovial sites, citrullinated RA-related antigens such as type II collagens, fibrin (ogen), vimentin, and α-enolase could be targeted by ACCPAs. Since ACCPA production can be initiated a long time before RA sign appearance, primary auto-immunization against these citrullinated proteins can be originated from extra-articular sites. It has been shown that there is a significant association between P. gingivalis periodontitis, anti- P. gingivalis antibodies, and RA. P. gingivalis gingipains (Rgp, Kgp) can degrade proteins such as fibrin and α-enolase into some peptides in the form of Arg in the C-terminal which is converted to citrulline by PPAD. Also, PPAD can citrullinate type II collagen and vimentins (SA antigen). P. gingivalis induces inflammation and chemoattraction of immune cells such as neutrophils and macrophages through the increase of C5a (gingipain C5 convertase-like activity) and SCFA secretion. Besides, this microorganism stimulates anoikis, a special type of apoptosis, and NETosis, an antimicrobial form of neutrophil death, leading to the release of PAD1-4, α-enolase, and vimentin from apoptotic cells into the periodontal site. In addition, gingipains can degrade macrophages CD14 and decrease their ability in apoptotic cell removal. Gingipains also can cleave IgGs in the Fc region and transform them into rheumatoid factor (RF) antigens. In the present study, the effects of P. gingivalis on rheumatoid arthritis autoimmune response have been reviewed, which could attract practical insight both in bench and clinic.

Functional interplay between long non-coding RNAs and Breast CSCs.

Breast cancer (BC) represents aggressive cancer affecting most women's lives globally. Metastasis and recurrence are the two most common factors in a breast cancer patient's poor prognosis. Cancer stem cells (CSCs) are tumor cells that are able to self-renew and differentiate, which is a significant factor in metastasis and recurrence of cancer. Long non-coding RNAs (lncRNAs) describe a group of RNAs that are longer than 200 nucleotides and do not have the ability to code for proteins. Some of these lncRNAs can be mainly produced in various tissues and tumor forms. In the development and spread of malignancies, lncRNAs have a significant role in influencing multiple signaling pathways positively or negatively, making them promise useful diagnostic and prognostic markers in treating the disease and guiding clinical therapy. However, it is not well known how the interaction of lncRNAs with CSCs will affect cancer development and progression.Here, in this review, we attempt to summarize recent findings that focus on lncRNAs affect cancer stem cell self-renewal and differentiation in breast cancer development and progression, as well as the strategies and challenges for overcoming lncRNA's therapeutic resistance.