Mechanisms of preventative and therapeutic role of probiotics in different allergic and autoimmune disorders

The prevalence of allergic and autoimmune diseases has been increasing from the last decades of 20th century. Intestinal microflora contributes to antigen exposure in early life and is one of the most abundant sources of early immune stimulation as well as adaptation. Because allergic and autoimmune responses manifest early in life, there has been obvious interest in the potential benefits of modifying the gastrointestinal flora by using probiotic supplementation. So far, there have been several studies to address the role of probiotics in primary prevention and therapy, with a reported suspicious reduction in the incidence of atopic and autoimmune diseases. Here, our aim is to evaluate the available knowledge of mechanisms of preventative and therapeutic role of probiotics in different allergic and autoimmune disorders. Promising mechanisms of probiotic effects may be categorized as local and systemic effects. Local influences of probiotics potentially include reduction of gut permeability and systemic penetration of antigens, increased local immunoglobulin A production, and alteration of local inflammation or tolerance induction. Some possible systemic effects consist of anti-inflammatory effects mediated by Th17 cells and Toll-like receptors, Th1 skewing of responses to allergens, activation of tolerogenic dendritic cells, in addition to T-regulatory cell production.

The roles of bone remodeling in normal hematopoiesis and age-related hematological malignancies

Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populations.Recent advances in intravital imaging has suggested that the expansion of hematopoietic stem cells(HSCs)and acute myeloid leukemia cells is restricted to bone marrow microdomains during a distinct stage of bone remodeling.These findings indicate that dynamic bone remodeling likely imposes additional heterogeneity within the BMME to yield differential clonal responses.A holistic understanding of the role of bone remodeling in regulating the stem cell niche and how these interactions are altered in age-related hematological malignancies will be critical to the development of novel interventions.To advance this understanding,herein,we provide a synopsis of the cellular and molecular constituents that participate in bone turnover and their known connections to the hematopoietic compartment.Specifically,we elaborate on the coupling between bone remodeling and the BMME in homeostasis and age-related hematological malignancies and after treatment with bone-targeting approaches.We then discuss unresolved questions and ambiguities that remain in the field.