Caerulomycin A inhibits Th2 cell activity: a possible role in the management of asthma

We have recently demonstrated that Caerulomycin A induces regulatory T cells differentiation by suppressing Th1 cells activity. The role of regulatory T cells is well established in suppressing the function of Th2 cells. Th2 cells are known to inflict the induction of the activation of asthma. Consequently, in the present study, we monitored the influence of Caerulomycin A in inhibiting the activity of Th2 cells and its impact in recuperating asthma symptoms. Interestingly, we observed that Caerulomycin A significantly suppressed the differentiation of Th2 cells, as evidenced by downregulation in the GATA-3 expression. Further, decline in the levels of IL-4, IL-5 and IL-13 cytokines and IgE was noted in the animals suffering from asthma. Furthermore, we noticed substantial suppression in the inflammatory response and number of eosinophils in the lungs. In essence, this study signifies an important therapeutic role of Caerulomycin A in asthma

Memory like NK cells display stem cell like properties after Zika virus infection.

NK cells have been shown to display adaptive traits such as memory formation akin to T and B lymphocytes. Here we show that Zika virus infection induces memory like NK cells that express CD27. Strikingly, these cells exhibit stem-like features that include expansion capacity, self-renewal pathway, differentiation into effector cells, longer telomeres and gene signature associated with hematopoietic stem cell (HSC) progenitors. This subset shared transcriptional and epigenetic changes with memory CD8 T cells, stem cells and stem like T cells. These NK cells with memory and stem cell features, which we term "NK memory stem cells", demonstrated greater antiviral potential than CD27- or naïve CD27+ NK when adoptively transferred to Zika infected mice. Our results also suggest a role for the transcription factor TCF-1 in memory and stemness features of this NK subset. This study defines a unique TCF1hi CD27+ NK subset with memory capacity and stem cell features that play a role in antiviral immunity

Costimulatory CD226 Signaling Regulates Proliferation of Memory-like NK Cells in Healthy Individuals with Latent <i>Mycobacterium tuberculosis</i> Infection

It is now widely accepted that NK cells can acquire memory, and this makes them more effective to protect against some pathogens. Prior reports indicate memory-like NK cells (mlNKs) in murine model of Mycobacterium tuberculosis (Mtb) as well as in healthy individuals with latent TB infection (LTBI). The increased expression of CD226 was evident in mlNKs from LTBI+ people after stimulation with γ-irradiated Mtb (γ-Mtb). We thus evaluated the contribution of costimulatory CD226 signaling in the functionality of mlNKs in LTBI+ people. We found that blockade of CD226 signaling using the antibody- or CRISPR/Cas9-mediated deletion of the CD226 gene in NK cells diminished the proliferation of mlNKs from LTBI+ people. Blocking CD226 signaling also reduced the phosphorylation of FOXO1 and cMyc expression. Additionally, cMyc inhibition using a chemical inhibitor reduced proliferation by mlNKs from LTBI+ people. Moreover, blocking CD226 signaling reduced glycolysis in NK cells, and the inhibition of glycolysis led to reduced effector function of mlNKs from LTBI+ people. Overall, our results provide a role for CD226 signaling in mlNK responses to Mtb

Caerulomycin A suppresses the differentiation of naïve T cells and alleviates the symptoms of experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is a highly detrimental autoimmune disease of the central nervous system. There is no cure for it but the treatment typically focuses on subsiding severity and recurrence of the disease. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS. It is characterized by frequent relapses due to the generation of memory T cells. Caerulomycin A (CaeA) is known to suppress the Th1 cells, Th2 cells, and Th17 cells. Interestingly, it enhances the generation of regulatory T cells (Tregs). Th1 cells and Th17 cells are known to aggravate EAE, whereas Tregs suppress the disease symptoms. Consequently, in the current study we evaluated the influence of CaeA on EAE. Intriguingly, we observed by whole body imaging that CaeA regressed the clinical symptoms of EAE. Further, there was reduction in the pool of Th1 cells, Th17 cells, and CD8 T cells. The mechanism involved in suppressing the EAE symptoms was due to the inhibition in the generation of effector and central memory T cells and induction of the expansion of Tregs. In essence, these findings implicate that CaeA may be considered as a potent future immunosuppressive drug