We have taken advantage of the Cre/lox system to generate a mouse model with inducible deficiency of transforming growth factor  receptor II (TRII). Using this approach, transforming growth factor  (TGF-) signaling deficiency can be restricted to the hematopoietic system by bone marrow transplantation. Mice that received transplants with TRII ؊/؊ bone marrow develop a lethal inflammatory disorder closely resembling that of TGF-1-null mice. Previous in vitro studies have suggested multiple roles for TGF- in T-cell development, including proliferation, apoptosis, and differentiation. We used our transplantation model to ask whether T-cell development is normal in the absence of TGF- signaling. The findings show for the first time in vivo and in fetal thymus organ culture (FTOC) that TGF- is not required for thymocytes to differentiate along the entire pathway of thymic T-cell development, as defined by the expression patterns of CD4, CD8, CD25, and CD44. In contrast to previous investigations, no increase of thymocyte apoptosis was observed. However, TRII-deficient CD8 ؉ thymocytes displayed a 2-fold increase in proliferation rate, as determined by bromodeoxyuridine ( IntroductionTransforming growth factor  (TGF-) is a group of growth factor isoforms (TGF1, TGF2, and TGF3) involved in a multitude of physiologic functions including the immune system. They primarily interact with the TGF- type I receptor (TRI) and type II receptor (TRII), both essential for propagation of the intracellular signal, including phosphorylation of Smad (small mother against decapentaplegic) proteins regulating transcriptional activation. The development of immature thymocytes to CD4 ϩ or CD8 ϩ singlepositive (SP) T cells is defined by their sequential expression of cell surface markers such as CD3, CD4, CD8, CD25, CD44, and the T-cell receptor (TCR). 1,2 Involvement of TGF- in T-cell function has been suggested by in vitro studies demonstrating that TGF- inhibits interleukin-1 (IL-1)-, IL-2-, and IL-7-dependent thymocyte proliferation. [3][4][5][6] Expansion of thymocytes may also be indirectly promoted by an inhibitory action of TGF- on apoptosis. [7][8][9] Inhibitory effect of TGF- on thymocyte development has been shown in fetal thymus organ culture (FTOC). 10 This study demonstrated that TGF- causes a very early block in development within the CD4 Ϫ CD8 Ϫ population, affecting differentiation of the CD44 ϩ CD25 Ϫ into the CD44 ϩ CD25 ϩ subset of thymocytes. Further evidence for an inhibitory mode of action on T-cell development derives from the observation that TGF- inhibits differentiation of CD4 ϩ thymocytes into the T helper 1 (Th1) and Th2 subsets of T helper cells. 11,12 A more complex immunoregulatory role of TGF- emerged by the finding that TGF- may also have stimulatory effects on immune functions. Thus, at certain stages of T-cell development, TGF- stimulates, rather than inhibits, proliferation. 13 A critical role of TGF- in T-cell homeostasis and function has been reinforced by studies using kn...
Background: Smartphones present a near-ubiquitous channel through which structured lifestyle change can reduce risk or progression of the most common noncommunicable diseases. We explored whether a digital structured lifestyle program enhances weight loss. Methods: We randomized overweight and obese participants attending a four-month lifestyle change program to either standard weekly coaching sessions (controls), or standard treatment supplemented with a digital therapeutic mobile application (intervention). Changes in body mass index after four months were the main outcome measure. Odds ratios of achieving 5% weight loss were estimated with unconditional logistic regression. Results: Of 234 eligible persons, 146 (62%) agreed to participate, were block-randomized, showed up for the baseline measures, and constituted the intention-to-treat (ITT) sample ( n = 95 intervention group, n = 51 control group). In the intervention group, 70 (74%) downloaded the mobile application and completed the program (intervention per-protocol). Significant weight loss and BMI reduction were observed for both the intention-to-treat intervention group ( P < 0.05, P = 0.01) and the per-protocol intervention group ( P < 0.0001, P < 0.0001). For the intervention per-protocol group, the odds ratio of achieving 5% weight loss, compared to not treated per-protocol, was 3.3 (95% CI 1.3-8.2), adjusting for age and weight at baseline.Attendance to weekly coaching sessions decreased by 18% during the program in the control group while it increased by 3% amongst the per-protocol group ( P = 0.004). Conclusions: These preliminary findings support the benefit of a digital therapeutic to enhance weight reduction and attendance in a structured lifestyle change program. Larger trials of longer duration are needed to confirm these findings.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.