Leukocyte Homing, Fate, and Function Are Controlled by Retinoic Acid

Abstract

Although vitamin A was recognized as an "anti-infective vitamin" over 90 years ago, the mechanism of how vitamin A regulates immunity is only beginning to be understood. Early studies which focused on the immune responses in vitamin A-deficient (VAD) animals clearly demonstrated compromised immunity and consequently increased susceptibility to infectious disease. The active form of vitamin A, retinoic acid (RA), has been shown to have a profound impact on the homing and differentiation of leukocytes. Both pharmacological and genetic approaches have been applied to the understanding of how RA regulates the development and differentiation of various immune cell subsets, and how RA influences the development of immunity versus tolerance. These studies clearly show that RA profoundly impacts on cell-and humoralmediated immunity. In this review, the early findings on the complex relationship between VAD and immunity are discussed as well as vitamin A metabolism and signaling within hematopoietic cells. Particular attention is focused on how RA impacts on T-cell lineage commitment and plasticity in various diseases.

Molecular mechanisms of reversing neural degeneration by retinoic acid, a major derivative of vitamin A

“…Alteration of retinoids in disease pathogenesis is also very peculiar to understand. Many molecular targets of therapeutics can be identified by scrutinizing intrinsic causes (Guo et al, 2015;Greena et al, 2016). Retinoid isomers inside cells are known to carry out gene activation mechanisms and transcription regulation.…”

“…Collectively, all vitamin A derivatives are called retinoids (Guo et al, 2015). Retinol is the primary type of retinoid found on the circulatory system (D' Ambrosio et al, 2011;Goodman and Blaner, 1984).…”

“…In addition, RA can be used against disease pathogenicity. Natural vitamin A deficit directly acts on nervous system and immune system causing adverse effects (Guo et al, 2015;Dawson et al, 2006;Imdad et al, 2010;Dupe et al, 2003). Further, experiments using transgenic model animals containing knockout RA utilizing genes have revealed that some phenotypes are lethal (Greena et al, 2016;Molotkov et al, 2002) while some model animals had disease pathogenic conditions.…”

“…Further, experiments using transgenic model animals containing knockout RA utilizing genes have revealed that some phenotypes are lethal (Greena et al, 2016;Molotkov et al, 2002) while some model animals had disease pathogenic conditions. For example, Raldha-2-transgenic mouse lines who cannot utilize all-trance retinoic acid or 9-cis retinoic acid are found to be a lethal phenotype (Guo et al, 2015). Therefore, RA is one of most important effector molecule in shaping tissue and organ systems.…”

“…Further, immunological diversity is controlled by RAR-ATRA receptor molecules by up regulating proteins needed for phenomena such as class switching and somatic hyper mutation (Cattoretti et al, 2006) while RAR-ATRA also helps in B cell maturation (Chen and Ross, 2007). In addition, RA paracrine signaling mechanisms allow cellular cross talking among leukocytes to overcome infectious conditions (Guo et al, 2015).…”