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TCRαβ+CD8αα+ intraepithelial lymphocytes (CD8αα+ αβ IELs) are a specialized subset of T cells in the gut epithelium that develop from thymic agonist selected IEL precursors (IELps). The molecular mechanisms underlying the selection and differentiation of this T cell type in the thymus are largely unknown. Here, we found that Bcl6 deficiency in αβ T cells resulted in the near absence of CD8αα+ αβ IELs. BCL6 was expressed by approximately 50% of CD8αα+ αβ IELs and by the majority of thymic PD1+ IELps after agonist selection. Bcl6 deficiency blocked early IELp generation in the thymus, and its expression in IELps was induced by thymic TCR signaling in an ERK-dependent manner. As a result of Bcl6 deficiency, the precursors of IELps among CD4+CD8+ double-positive thymocytes exhibited increased apoptosis during agonist selection and impaired IELp differentiation and maturation. Together, our results elucidate BCL6 as a crucial transcription factor during the thymic development of CD8αα+ αβ IELs. Editor's summary: Intraepithelial lymphocytes (IELs) reside within the intestinal epithelium, where they regulate immune tolerance. Unconventional CD8αα+ αβ IELs are selected from thymic IEL precursors (IELps) after strong TCR signaling; however, the transcription factors governing this process of agonist selection are not well defined. Xing et al. found that mice lacking the transcription factor BCL6 in αβ T cells almost did not develop CD8αα+ αβ IELs. Thymic IELps up-regulated BCL6 after TCR stimulation, and BCL6 expression was required for their survival, differentiation, and maturation. These findings identify that BCL6 is required for the development of unconventional CD8αα+ αβ IELs during agonist selection. —Hannah Isles [ABSTRACT FROM AUTHOR]

Objective To explore the application value of the modified UPOINT typing system in the treatment of patients with type HI prostatitis. Methods Total of 154 patients with type HI prostatitis from March 2022 to March 2023 were enrolled in the study. According to the random number table method, they were divided into the observation group and the control group, 77 cases each. The patients were classified and treated individually according to the modified UPOINT typing system and the traditional UPOINT typing system. The National Institutes of Health chronic prostatitis symptom index ( NIH-CPSI), International Index of Erectile Function ( IIEF-5 ), Generalized Anxiety Disorder ( GAD-7 ), Patien Health Questionnare (PHQ-9) were used to evaluate the therapeutic effects of the two groups. Results After treatment, the pain and discomfort, urination discomfort, quality of life subscores, NIH-CPSI total score, GAD-7 and PHQ-9 scores of patients in two groups were all significantly decreased, the IIEF-5 score was significantly increased (P <0. 05), but the IIEF-5 score inthe observation group was increased more significantly (P <0.05). Conclusion Therapeutic regime based on the modified UPOINT typing system is helpful to improve the individualized treatment of type HI prostatitis patients and ED, which is worthy of clinical application and promotion. [ABSTRACT FROM AUTHOR]

TCRαβ + CD8αα + intraepithelial lymphocytes (CD8αα + αβ IELs) are a specialized subset of T cells in the gut epithelium that develop from thymic agonist selected IEL precursors (IELps). The molecular mechanisms underlying the selection and differentiation of this T cell type in the thymus are largely unknown. Here, we found that Bcl6 deficiency in αβ T cells resulted in the near absence of CD8αα + αβ IELs. BCL6 was expressed by approximately 50% of CD8αα + αβ IELs and by the majority of thymic PD1 + IELps after agonist selection. Bcl6 deficiency blocked early IELp generation in the thymus, and its expression in IELps was induced by thymic TCR signaling in an ERK-dependent manner. As a result of Bcl6 deficiency, the precursors of IELps among CD4 + CD8 + double-positive thymocytes exhibited increased apoptosis during agonist selection and impaired IELp differentiation and maturation. Together, our results elucidate BCL6 as a crucial transcription factor during the thymic development of CD8αα + αβ IELs.

The diagnosis of bone metastasis of prostate cancer (PC) is of great significance to the treatment and prognosis of patients with PC.Bone scan is the most commonly used in the early diagnosis of bone metastasis, but its specificity is low and there is a high false positive.In recent years, with the in-depth study of the application of CT, MRI, emission computed tomography (ECT), positron emission computed tomography/computed tomography (PET/CT) and deep learning algorithm-convolutional neural networks (CNN) in the diagnosis of bone metastasis, the combined application of various auxiliary parameters in the diagnosis of bone metastasis has significantly been improved. The therapeutic effect of PC patients with bone metastasis can also be evaluated, which is expected to achieve the treatment of bone metastasis as well as diagnosis. By systematically expounding the research progress of the above-mentioned techniques in the diagnosis of bone metastasis, it can provide clinicians with new methods for the diagnosis of bone metastasis and improve the diagnostic efficiency for bone metastasis.