Retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of mucosal immunity during DNA vaccination

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Couple things here, this is retinoic acid metabolism btw.

Retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of mucosal immunity during DNA vaccination

Retinaldehyde dehydrogenase 2 as a molecular adjuvant for enhancement of...

RALDH2 can be used as an alternative adjuvant to ATRA during DNA vaccination leading to an increase in both systemic and mucosal T cell immunity and better protection at mucosal sites.

Dendritic cells (DCs) from the gut-associated lymphoid organs produce RA and imprint T cells with gut-homing potential [14, 21]. The administration of ATRA, the major metabolic derivative of vitamin A, has been shown to act physiologically to induce expression of gut-homing receptors on lymphocytes [11]. Unfortunately, ATRA is practically insoluble in water, which precludes its inclusion in many vaccines [22].

In this study we are transfecting epithelial cells with a RALDH2 DNA construct using an intramuscular-electroporation regime with the final objective of increasing mucosal-homing T cells and protection against viral challenge. We hypothesized that RA produced by transfected muscle epithelial cells could imprint DCs that traffic to the site of immunization with a mucosal phenotype (i.e. the ability to produce RA themselves). Alternatively, transfected DCs can be conditioned to produce RA and present the vaccine antigen in draining lymph nodes, the RA they produce should then instruct the responding lymphocytes to migrate to mucosal tissues.

Our results demonstrate that RALDH2 immunization increases systemic responses and protects from future mucosal viral challenge. A similar effect has been previously observed when ATRA is used as an adjuvant

Just a strange observation about myself involving white blood cells

In a microbio class of 12 students, we were doing skin-pricks of our fingers with mini-lancets and viewing Wright’s-stained droplets of our own blood under the microscope with the intention of finding and identifying several types of white blood cell. [image] I had ONE measly lymphocyte on the entire slide, while every other student had dozens of various WBCs. The instructor scanned the slide herself and made the statement that she had never seen that in her ~5 years of teaching this class or …

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Age-Dependent Decrease in the Induction of Regulatory T Cells Is Associated With Decreased Expression of RALDH2 in Mesenteric Lymph Node Dendritic Cells

Age-Dependent Decrease in the Induction of Regulatory T Cells Is Associated...

[guitarman01]

Male mice treated with antiandrogens exhibited increased disease incidence and severity, and decreased CD103DC function including a decreased ability to induce conversion of Tregs in vitro and decreased expression of RALDH2 mRNA.

we found that male microbiota may protect, in part, via an effect on tolerogenic CD103+ dendritic cells (CD103DC) that induce peripheral Tregs (pTregs) through TGFβ and retinoic acid (RA) production.

Still looking at dosage and duration for possible treatment.
Amazon has not been able to keep this in stock and now they have raised the price because of demand unfortunately.
This could be a type of immune priming or training that starts from birth.

Has the microbiota played a critical role in the evolution of the adaptive immune system?

Summary

B. infantis 35624 has been previously shown to protect against inflammatory disease in a number of murine models (including colitis, arthritis, respiratory allergy and infection models). Adoptive transfer of CD25+ T cells from B. infantis-fed animals to naive recipients transferred the anti-inflammatory protective effect. In humans, we now describe that consumption of this bacterium results in elevated IL-10 responses and Foxp3 expression. Manipulation of T regulatory cell numbers or functions is an exciting therapeutic target in a wide range of inflammatory disorders. This data confirms our in vitro and murine models. However, we made the surprising discovery that B. infantis 35624 induces the immune-regulatory enzyme RALDH2 in dendritic cells and the product of this enzyme, retinoic acid, was essential for the induction of regulatory T cells. Thus, a formulation which combines the substrate, i.e. vitamin A or its derivatives, with a bacterial strain that induces expression of the enzyme responsible for substrate conversion will ensure the optimal conversion of the substrate to its immunologically active product. This formulation will provide a profound therapeutic benefit in patients suffering from inflammatory disorders. The formulation may be useful in maintaining a normal structure and function of the skin and mucous membranes (such as in the lung, intestines, nose, eyes and female reproductive tract).

Inhibiting Vitamin A Metabolism As An Approach To Male Contraception

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