Pharmacologically oral supplementation of IAP prevents antib

Pharmacologically, oral supplementation of IAP prevents antibiotic-induced susceptibility to enteric pathogens such as Salmonella Typhimurium, and Clostridium difficile (Malo et al., 2010; Alam et al., 2014). We have shown that oral IAP supplementation not only prevents but also cures the high fat diet-induced metabolic syndrome in mice (Kaliannan et al., 2013). IAP supplementation have been shown to have efficacious values in treating colitis in humans and mice (Lukas et al., 2010; Ramasamy et al., 2011; Whitehouse et al., 2010), and peritonitis in animal models (van Veen et al., 2005; Ebrahimi et al., 2011). We have previously shown that IAP deficiency causes T2DM in mice (Kaliannan et al., 2013), and here we demonstrate that IAP deficiency is associated with T2DM in humans. We strongly believe that IAP deficiency also causes T2DM in humans, and to confirm this hypothesis, we anticipate, it will require a long-term cohort study monitoring ‘temporal IAP profiles’ and incidence rates of T2DM among the people with ‘incipient diabetes’ and other healthy populations.
Conclusions
Author Contribution
Conflict of Interests
Acknowledgments The study was supported by a grant (HB.1401) from Harvard Biotech BD Ltd., Dhaka, Bangladesh (to M.S.M). We are thankful to Jagannath Malo and Gopal Chandra for their technical assistance including data collection and biochemical analyses. We are grateful to Syed S. Islam, MD, PhD (Epidemiology) for his critical review of the statistical analysis as well as the manuscript.
Introduction Type 1 diabetes (T1D) is a major global health issue, and its incidence is increasing. T1D is a T cell-mediated autoimmune disease that reduces the population of pancreatic islet β cells, which limits insulin production and interferes with glucose homeostasis. The immune dysfunction in T1D is complicated, with effects both in pancreatic islets and outside the pancreas. Different components of the immune system [e.g., CD4+, CD8+ T cells, Tregs, B cells, dendritic ANA 12 (DCs), monocyte/macrophages (Mo/Mϕs), natural killer T cells (NKTs)] contribute to autoimmune responses in T1D, complicating efforts to develop successful treatments or a cure that will work across most or all individuals with the disease. Several recent clinical trials (Bach, 2011; Wherrett et al., 2011) highlight the challenges in conquering T1D, but their failures provide some valuable lessons about the limitations of conventional immune therapy and the future direction of the quest. Specifically, they point to the need for an approach that produces comprehensive immune modulation at both the local pancreatic and systematic levels rather than targeting the pancreatic effects of one or a few components of the immune system. The Stem Cell Educator therapy takes this broader approach (Zhao and Mazzone, 2010; Zhao et al., 2012; Zhao, 2012; Zhao et al., 2013; Li et al., 2015). Physiologically, the human immune system constantly protects the body against a variety of pathogens that may be encountered. Following the recognition and eradication of pathogens through adaptive immune responses, the majority (90–95%) of T cells undergo apoptosis with the remaining cells forming a pool of memory T cells, designated central memory T cells (TCM), effector memory T cells (TEM), and resident memory T cells (TRM) (Clark, 2015). In comparison to conventional T cells, these memory T cells are long-lived with distinct phenotypes, such as expression of specific surface markers, rapid production of different cytokine profiles, capability of direct effector cell function, a different potential for proliferation, and unique homing distribution patterns. As a group, memory T cells display quick reactions upon re-exposure to their cognate antigens in order to eliminate the reinfection of pathogens and restore balance and harmony of the immune system. Nevertheless, increasing evidence establishes that autoimmune memory T cells become the “stumbling blocks” and hinder most attempts to treat or cure autoimmune diseases, including T1D, multiple sclerosis (MS), rheumatoid arthritis (RA), and system lupus erythematosus (SLE) (Ehlers and Rigby, 2015; Clark, 2015; Devarajan and Chen, 2013). Therefore, novel and more comprehensive approaches are needed to fundamentally correct the inordinate dominance of autoimmune T cell memory and overcome the complexities of autoimmune responses.