Unraveling the autoimmune translational research process layer by layer

Abstract

Autoimmune diseases have a complex etiology and despite great progress having been made in our comprehension of these disorders, there has been limited success in the development of approved medications based on these insights. Development of drugs and strategies for application in translational research and medicine are hampered by an inadequate molecular definition of the human autoimmune phenotype and the organizational models that are necessary to clarify this definition.

Artery Tertiary Lymphoid Organs Contribute to Innate and Adaptive Immune Responses in Advanced Mouse Atherosclerosis

“…These are governed by territorialized cytokine-driven differentiation and transdifferentiation pathways shaping and programming highly specialized immune cell phenotypes in peripheral tissues in response to antigen and inflammatory cues. However, the immune system may be overwhelmed and become exhausted when the antigen load proceeds unimpaired, 38 such as in chronic infection, during graft rejection, in certain types of cancer, in autoimmune Well-structured artery tertiary lymphoid organs (ATLOs) arise adjacent to advanced atherosclerotic plaques in the abdominal aorta of aged Apoe -/-mice. Cellularity, structures, and the territoriality of ATLO neogenesis indicate comprehensive T-and B-cell responses toward unknown arterial wall-derived autoantigens although these responses seem to maintain a balance between pro-and anti-inflammatory participants of both innate and adaptive immunity.…”

“…Translation of findings in experimental models and those observed in animal models of atherosclerosis to human diseases remains a major challenge. 38 6,7,[87][88][89][90][91][92][93] When the immune cell composition of SLOs and ATLOs are compared with that of atherosclerotic plaques, major differences become apparent: Plaques have a rather limited set of immune cells (Figures 2 and 3). In addition, lymphocyte recirculation of adoptively transferred T cells is dramatically higher in ATLOs or SLOs when compared with plaques.…”

Priorities for Cardiovascular Outcomes Research

“…The 4 steps (T1-T4) in the translation of laboratory discovery science (T0) into clinical settings need to be optimized, ranging from the translation of bench to humans (T1), to clinical trials (T2), to practice (T3), and to community health (T4). [49][50][51] Regarding the latter steps, the NHLBI has organized internal retreats to discuss the dilemmas of doing more timely and meaningful research and has made a commitment to support T3/T4 translation research, focusing specifically on dissemination and implementation science. 52,53 Their strategic vision is to sustain investigator-initiated portfolios; establish collaborative, iterative processes with our communities; identify critical knowledge gaps and compelling questions; and outline strategies for future investment of research dollars.…”

Process evaluation and proximal impact of an affect-based exercise intervention among adolescents

“…To advance the knowledge thus gained toward being applied in a community setting, where population-level outcomes may be observed, it is necessary to move these interventions out of the laboratory. As described by Blumberg et al [31], the later phases of the translational research continuum (T3/T4) represent the translation of new data acquired through controlled clinical studies into practice in the community. This study represents the translation of laboratorybased studies on the associations between exercise intensity, exercise-associated affect, and physical activity participation into an investigation of a community-based intervention with the potential to impact large numbers of adolescents.…”