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In the past few years, huge advances have been made in techniques to analyse cells at an individual level using RNA sequencing, and many of these have precipitated exciting discoveries in the immunology of type 1 diabetes (T1D). This review will cover the first papers to use scRNAseq to characterise human lymphocyte phenotypes in T1D in the peripheral blood, pancreatic lymph nodes and islets. These have revealed specific genes such as IL-32 that are differentially expressed in islet –specific T cells in T1D. scRNAseq has also revealed wider gene expression patterns that are involved in T1D and can predict its development even predating autoantibody production. Single cell sequencing of TCRs has revealed V genes and CDR3 motifs that are commonly used to target islet autoantigens, although truly public TCRs remain elusive. Little is known about BCR repertoires in T1D, but scRNAseq approaches have revealed that insulin binding BCRs commonly use specific J genes, share motifs between donors and frequently demonstrate poly-reactivity. This review will also summarise new developments in scRNAseq technology, the insights they have given into other diseases and how they could be leveraged to advance research in the type 1 diabetes field to identify novel biomarkers and targets for immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Analyzing Hematological parameters is usually in use to monitor various circumstances such as infection, inflammation and anemia. For that we studied blood parameters which are in touch with immunized laboratory animals (rabbits) after immunizing these animals with Corynebacterium pseudotuberculosis then used an adjuvant of Pseudomonas aeruginosa to stimulate the immune response cells after 2 to 3 weeks of immunization. Different concentrations were used to examine the effect on the animals' blood parameters changing. Methods: Corynebacterium pseudotuberculosis bacterium was used at current study for evaluating the effect of immunizing laboratory rabbits with two different immune stimulators working together as adjuvant on the blood picture with the aid of 12 breed rabbits from different genders, dividing them at the base of inoculation with pre-killed and sonicated cells of bacteria (antigens) onto 4 categories as following: the group-1 members of rabbits were injected with the antigen, group-2 and group-3 included rabbits injected with the two inoculations at various concentrations; final group, group-4 was the control group. Results: Thus, white blood cells known to be our main line of defenses act firstly in our body towards different infecting microorganisms, their count always was increased through the immunization correlated with other measured parameters. From the results we can see that the lymphocytes percentage had no alteration between the infected and the immunized compared to control group, while the percentage of MID that refers to the monocytes was at the same range in both infected and the immunized control rabbit's groups. Granulocyte cells percentage, which is including heterophilic, basophilic and eosinophilic cells, was significantly decreased (P>0.05) compared with control at all groups. Conclusion: We conclude that C. pseudotuberculosis might function as a potent immunogen to notice the complete blood picture variations. [ABSTRACT FROM AUTHOR]

Highlights: What are the main findings? CD39-CD73 axis in tumor-associated immune cells promotes immune exhaustion, impairment of antitumor immune activity, and increased CRC progression. CD73 overexpression in cancer cells is associated with tumor growth, chemoresistance, and decreased patient survival. Extracellular ATP exhibits dual effects, either reducing tumor cell proliferation or favoring chemoresistance in a concentration-dependent fashion. Purinergic signaling components exhibit prognostic value and have the potential to be utilized as therapeutic targets. What is the implication of the main finding? CD73 induces colorectal cancer progression. CD39 contributes to immunosuppressive activity of T cells and poor prognosis. P2 and P1 purinoceptors were mainly associated with poor prognosis for patients. Ectonucleotidases and purinoceptors have potential as therapeutic targets in CRC. Simple Summary: Colorectal cancer is a leading cause of cancer-related death. Activated immune cells have the potential to eliminate tumor cells, but cancers gain the ability to suppress immune cell functions and escape immune attack. We explored one mechanism that cancers use to evade immune cells in colorectal cancer. This mechanism alters levels of molecules known as purines. Purines are key players in cellular energetics and many cellular processes and can also lead to immune suppression in cancer. In this study, we reviewed the literature that identified specific enzymes (ectonucleoetidases) and receptors (purinoceptors) which alter the levels of purines and contribute to immunosuppression in colorectal cancer. We hope that targeting these enzymes and receptors can activate the immune response against colorectal cancer and halt cancer growth and progression. Colorectal cancer (CRC) is among the most common cancers and exhibits a high fatality rate. Gut inflammation is related to CRC, with loss of homeostasis in immune cell activities. The cells of the innate and adaptive immune system, including macrophages, neutrophils, mast cells, and lymphocytes, are present in most solid tumors. Purinergic signaling allows for communication between immune cells within the tumor microenvironment (TME) and can alter the TME to promote tumor progression. This system is regulated by the availability of extracellular purines to activate purinoceptors (P1 and P2) and is tightly controlled by ectonucleotidases (E-NPP, CD73/CD39, ADA) and kinases, which interact with and modify nucleotides and nucleosides availability. In this review, we compiled articles detailing the relationship of the purinergic system with CRC progression. We found that increased expression of CD73 leads to the suppression of effector immune cell functions and tumor progression in CRC. The P1 family purinoceptors A1, A2A, and A2B were positively associated with tumor progression, but A2B resulted in increased cancer cell apoptosis. The P2 family purinoceptors P2X5, P2X7, P2Y2, P2Y6, and P2Y12 were factors primarily associated with promoting CRC progression. In summary, CD39/CD73 axis and the purinergic receptors exhibit diagnostic and prognostic value and have potential as therapeutic targets in CRC. [ABSTRACT FROM AUTHOR]