Murine CD4⁺CD25^- cells activated <it>in vitro</it> with PMA/ionomycin and anti-CD3 acquire regulatory function and ameliorate experimental colitis <it>in vivo</it>

<p>Abstract</p> <p>Background</p> <p>Induced regulatory T (iTreg) lymphocytes show promise for application in the treatment of allergic, autoimmune and inflammatory disorders. iTreg cells demonstrate advantages over natural Treg (nTreg) cells in terms of increased number of starting population and greater potential to proliferate. Different activation methods to generate iTreg cells result in iTreg cells that are heterogeneous in phenotype and mechanisms of suppression. Therefore it is of interest to explore new techniques to generate iTreg cells and to determine their physiological relevance.</p> <p>Methods</p> <p>Using phorbol myristate acetate (PMA)/ionomycin and anti-CD3 activation of CD4⁺CD25^- cells we generated <it>in vitro</it> functional CD4⁺CD25⁺ iTreg (TregPMA) cells. Functionality of the generated TregPMA cells was tested <it>in vivo</it> in a mouse model of inflammatory bowel disease (IBD) - CD45RB transfer colitis model.</p> <p>Results</p> <p>TregPMA cells expressed regulatory markers and proved to ameliorate the disease phenotype in murine CD45RB transfer colitis model. The body weight loss and disease activity scores for TregPMA treated mice were reduced when compared to diseased control group. Histological assessment of colon sections confirmed amelioration of the disease phenotype. Additionally, cytokine analysis showed decreased levels of proinflammatory colonic and plasma IL-6, colonic IL-1 β and higher levels of colonic IL-17 when compared to diseased control group.</p> <p>Conclusions</p> <p>This study identifies a new method to generate <it>in vitro</it> iTreg cells (TregPMA cells) which physiological efficacy has been demonstrated <it>in vivo</it>.</p

Arterial Ischemic Stroke in Children: Risk Factors and Etiologies

Stroke is increasingly recognized as a significant cause of morbidity or mortality in children and as a financial burden for families and society. Recent studies have identified and confirmed presumptive risk factors and have identified novel associations with childhood arterial ischemic stroke. A better understanding of these risk factors for stroke in children, which differ from the atherosclerotic risk factors in adults, is the first step needed to improve strategies for stroke prevention and intervention and ultimately minimize the physical, mental and financial burden of AIS. Here, we discuss recent advances in research for selected childhood stroke risk factors, highlighting the progress made in our understanding of etiologic mechanisms and pathophysiology, and address the future directions for acute and long-term treatment strategies for pediatric stroke