Stress-Induced Despair Behavior Develops Independently of the AHR-RORgt Axis in CD4+ cells

Current treatments for major depressive disorder are limited to neuropharmacological approaches and are ineffective for large numbers of patients. Recently, alternative means have been explored to understand the etiology of depression. Specifically, changes in the microbiome and immune system have been observed in both clinical settings and in mouse models. As such, microbial supplements and probiotics have become a target for potential therapeutics. A current hypothesis for the mechanism of action of these supplements is via the aryl hydrocarbon receptor’s (AHR) modulation of the T helper 17 cell (Th17) and T regulatory cell axis. As inflammatory RORgt+ CD4+ Th17 T cells and their primary cytokine IL-17 have been implicated in the development of stress-induced depression, the connection between stress, the AHR, Th17s and depression remains critical to disease understanding. Here, we utilize genetic knockouts to examine the role of the microbial sensor AHR in the development of stress induced despair behavior. We observe an AHR-independent increase in gut-associated Th17s in stressed mice, indicating that AHR is not responsible for this communication. Further, we utilized a CD4-specific Rorc knockout line to disrupt the production of Th17s. Mice lacking Rorc induced IL-17 did not show any differences in behavior from controls before or after stress. Finally, we utilize an unsupervised machine learning system to examine minute differences in behavior that could not be observed in traditional behavioral assays. Our data demonstrate that neither CD4 specific Ahr nor Rorc are necessary for the development of stress-induced anxiety-or depressive-like behaviors. These data suggest that research approaches should focus on other sources or sites of IL-17 production in stress-induced depression.

Vitamin D and immunomodulation in the skin: a useful affirmative nexus

Skin is the largest organ of the body having multifunctional activities. It has a dynamic cellular network with unique immunologic properties to maintain defensive actions, photoprotection, immune response, inflammation, tolerogenic capacity, wound healing, etc. The immune cells of the skin exhibit distinct properties. They can synthesize active vitamin D [1,24(OH)2D3] and express vitamin D receptors. Any difficulties in the cutaneous immune system cause skin diseases (psoriasis, vitiligo, atopic dermatitis, skin carcinoma, and others). Vitamin D is an essential factor, exhibits immunomodulatory effects by regulating dendritic cells’ maturation, lymphocytes’ functions, and cytokine production. More specifically, vitamin D acts as an immune balancing agent, inhibits the exaggeration of immunostimulation. This vitamin suppresses T-helper 1 and T-helper 17 cell formation decreases inflammatory cytokines release and promotes the maturation of regulatory T cells and interleukin 10 secretion. The deficiency of this vitamin promotes the occurrence of immunoreactive disorders. Administration of vitamin D or its analogs is the therapeutic choice for the treatment of several skin diseases.