Compromised melanocyte survival due to decreased suppression of CD4+ & CD8+ resident memory T cells by impaired TRM-regulatory T cells in generalized vitiligo patients.

Regulatory T cells (Tregs) are involved in the suppression of activated T cells in generalized vitiligo (GV). The study was aimed to investigate resident memory (TRM)-Tregs and antigen-specific Tregs' numbers and functional defects in 25 GV patients and 20 controls. CD4+ & CD8+ TRM cell proliferation was assessed by BrDU assay; production of IL-10, TGF-ß, IFN-γ, perforin and granzyme B were assessed by ELISA and enumeration of TRM cells was done by flowcytometry. GV patients showed significantly increased frequency and absolute count of CD4+ & CD8+ TRM cells in lesional (L), perilesional (PL) and non-lesional (NL) skin compared to controls (p = 0.0003, p = 0.0029 & p = 0.0115, respectively & p = 0.0003, p = 0.003 & p = 0.086, respectively). Whereas, TRM-Treg (p < 0.0001 & p = 0.0015) and antigen-specific Tregs (p = 0.0014 & p = 0.003) exhibited significantly decreased frequency and absolute counts in L & PL skin. GV patients showed reduced suppression of CD8+ & CD4+ TRM cells (with increased IFN-γ, perforin & granzyme B) and decreased TRM-Tregs and antigen-specific Tregs (with decreased IL-10 & TGF-ß production) and reduced proliferation of SK-Mel-28 cells in co-culture systems. Immunohistochemistry revealed increased expression of TRM stimulating cytokines: IL-15 & IL-17A and reduced expression of TGF-ß & IL-10 in L, PL, NL skins compared to controls. These results for the first time suggest that decreased and impaired TRM-Tregs and antigen-specific Tregs are unable to suppress CD4+ & CD8+ TRMs' cytotoxic function and their proliferation due to decrease production of immunosuppressive cytokines (IL-10 & TGF-ß) and increased production of TRM based IFN-γ, perforin and granzyme B production, thus compromising the melanocyte survival in GV.

Salt-tolerant bacteria enhance the growth of mung bean (Vigna radiata L.) and uptake of nutrients, and mobilize sodium ions under salt stress condition.

Salinity is one of the significant abiotic stresses that exert harmful effects on plant growth and crop production. It has been reported that the harmfulness of salinity can be mitigated by the use of salt-tolerant plant growth-promoting (PGP) bacteria. In this study, four bacteria were selected from a total of 30 cultures, based on salt-tolerant and PGP properties. The isolates were found to produce indole acetic acid (8.49-19.42 µg/ml), siderophore (36.04-61.77%), and solubilize potassium and inorganic phosphate. Identification based on 16S rRNA gene sequencing revealed that the isolates belonged to Cronobacter (two isolates) and Enterobacter (two isolates). Inoculation of PGP bacteria under 2 and 10% salinity stress showed enhanced plant growth parameters in Vigna radiata compared to both salinity and non-salinity control plants. The rate of germination (113.32-206.64%), root length (128.79-525.31%), shoot length (34.09-50.32%), fresh weight, and dry weight were 3-fold higher in bacteria-treated seeds than control plants. The estimation of chlorophyll (1-5-fold), carotenoids (1-4-fold), and proline content (3.65-14.45%) was also higher compared to control plants. Further, the bacterized seeds showed enhanced nitrogen and phosphorous uptake and mobilized sodium ions from roots to leaves. Overall the strains SS4 and SS5 performed well in both 2 and 10% salt-amended soils. These strains could be formulated as a bioinoculant to mitigate the salinity stress in salinized soils.

Salinity severely affects the growth and productivity of Vigna radiate (mung bean) worldwide. Approximately 50 mM concentration of NaCl can cause >60% yield loss of mung bean. In this study, inoculation of salt-tolerant root nodule-associated plant growth-promoting bacteria showed 2­3-fold enhancements in mung bean plant growth, biomass, and physiology even at 2 and 10% salinity stress. Further, the inoculated mung bean plants showed an increment in the uptake of nitrogen and phosphorous in the salinized conditions and mobilized the Na⁺ ions from root to shoot to reduce the toxicity posed by Na⁺ ions. Therefore the strains identified in this study could be formulated to mitigate the salinity stress and improve the mung bean growth in salinized soils.

Emerging role of Tissue Resident Memory T cells in vitiligo: From pathogenesis to therapeutics.

Vitiligo is an acquired depigmenting disorder which affects both skin and mucous membranes and autoimmunity has been strongly suggested to play a role in loss of melanocytes. The recurrence of skin macules at the same sites where they were observed prior to the treatment, suggests the existence of Tissue Resident Memory T cells (TRMs) that persist within the skin or peripheral tissues with a longer survivability. Emerging studies have shown that reactivation of these skin TRMs results into autoreactive TRM cells in various autoimmune diseases including vitiligo. This review focuses on different subsets (CD8+ TRMs and CD4+ TRMs) of TRM cells, their retention and survivability in the skin along with their pathomechanisms leading to melanocyte death and progression of vitiligo. In addition, the review describes the TRM cells as potential targets for developing effective therapeutics of vitiligo.

Pathophysiology and recent therapeutic insights of sickle cell disease.

Sickle cell disease (SCD) is an autosomal recessive blood disorder which occurs due to point mutation in the ß-globin chain of hemoglobin. Since the past decades, various therapies have been put forth, which are based on obstructing pathophysiological mechanisms of SCD including inhibition of Gardos channel and cation fluxes which in turn prevents sickle erythrocyte destruction and dehydration. The pharmacological approaches are based on the mechanism of reactivating γ-globin expression by utilizing fetal hemoglobin (HbF)-inducing drugs such as hydroxyurea. In SCD, gene therapy could be considered as a promising tool which involves modifying mutation at the gene-specific target by either promoting insertion or deletion of globins. Although there are various therapies emerged so far in the treatment of SCD, many of them have faced a major setback in most of developing countries in terms of cost, unavailability of expertise, and suitable donor. Therefore, in addition to pathophysiological aspects, this review will discuss new advancements and approaches made in the therapeutic domain of SCD including a viewpoint of modulating hemoglobin in SCD by the intervention of probiotics.