CXCL13 is a chemokine that plays an important role in the regulation and development of secondary lymphoid organs. CXCL13 is also involved in the regulation of pathological processes, particularly inflammatory responses, of many diseases. The function of CXCL13 varies depending on the condition of the host. In a healthy condition, CXCL13 is mainly secreted by mouse stromal cells or human follicular helper T cells, whereas in diseases conditions, they are produced by human peripheral helper T cells and macrophages in non-lymphoid tissues; this is termed ectopic expression of CXCL13. Ectopic CXCL13 expression is involved in the pathogenesis of various immune-mediated inflammatory diseases as it regulates the migration of B lymphocytes, T lymphocytes, and other immune cells in inflammatory sites as well as influences the expression of inflammatory factors. Additionally, ectopic expression of CXCL13 plays a key role in ectopic lymphoid organ formation. In this review, we focused on the sources of CXCL13 in different conditions and its regulatory mechanisms in immune-mediated inflammatory diseases, providing novel ideas for further research on targeting CXCL13 for the treatment of immune-mediated inflammatory diseases.

The microdeletions of azoospermia factor (AZF) genes in Y chromosome are greatly associated with male infertility, which is also known as the second major genetic cause of spermatogenetic failure. Accumulating studies demonstrate that the different type of AZF microdeletions in patients reflect different clinical manifestations. Therefore, a better understanding of Y chromosome microdeletions might have broad implication for men health. In this study, we sought to determine the frequency and the character of different Y chromosome microdeletion types in infertile men in southwest of China. In total, 1274 patients with azoospermia and oligozoospermia were recruited in southwest of China and screening for Y chromosome microdeletions in AZF regions by multiplex polymerase chain reaction. The incidence of AZF microdeletions in southwest of China is 12.87%, which is higher than the national average. Further investigations unveiled that azoospermia factor c (AZFc) is the most frequent type of all the AZF microdeletions. Additionally, the number and also the quality of sperm in patients with AZFc microdeletion is decreasing with the age. Therefore, it is conceivable that the early testing for Y chromosome microdeletions in infertile men is crucial for fertility guidance. The early detection of Y chromosome microdeletions in infertile men can not only clearly explain the etiology of oligzoospermia and azoospermia, but also help for the clinical management of both infertile man and his future male offspring.

Amlexanox (ALX) is a small-molecule drug for the treatment of inflammatory, autoimmune, metabolic, and tumor diseases. At present, there are no studies on whether ALX has a therapeutic effect on inflammatory bowel disease (IBD). In this study, we used a mouse model of dextran sulfate sodium-induced colitis to investigate the effect of ALX-targeted inhibition of TBK1 on colitis. We found that the severity of colitis in mice was correlated with TBK1 expression. Notably, although ALX inhibited the activation of the TBK1-NF-κB/TBK1-IRF3 pro-inflammatory signaling pathway, it exacerbated colitis and reduced survival in mice. The results of drug safety experiments ruled out a relationship between this exacerbating effect and drug toxicity. In addition, ELISA results showed that ALX promoted the secretion of IL-1β and IFN-α, and inhibited the production of cytokines IL-6, TNF-α, IL-10, TGF-β, and secretory IgA. Flow cytometry results further showed that ALX promoted T-cell proliferation, activation, and differentiation, and thus played a pro-inflammatory role; also, ALX inhibited the generation of dendritic cells and the polarization of macrophages to M1 type, thus exerting anti-inflammatory effect. These data suggest that the regulation of ALX on the function of different immune cells is different, so the effect on the inflammatory response is bidirectional. In conclusion, our study demonstrates that simply inhibiting TBK1 in all immune cells is not effective for the treatment of colitis. Further investigation of the anti-inflammatory mechanism of ALX on dendritic cells and macrophages may provide a new strategy for the treatment of IBD.

TANK-binding kinase 1 (TBK1) is a key signaling kinase involved in innate immune and inflammatory responses. TBK1 drives immune cells to participate in the inflammatory response by activating the NF-κB and interferon regulatory factor signaling pathways in immune cells, promoting the expression of pro-inflammatory genes, and regulating immune cell function. Thus, it plays a crucial role in initiating a signaling cascade that establishes an inflammatory environment. In inflammation-related diseases, TBK1 acts as a bridge linking inflammation to immunity, metabolism, or tumorigenesis, playing an important role in the pathogenesis of immune-mediated inflammatory diseases, metabolic, inflammatory syndromes, and inflammation-associated cancers by regulating the activation of inflammatory pathways and the production of inflammatory cytokines in cells. In this review, we focused on the mechanisms of TBK1 in immune cells and inflammatory-related diseases, providing new insights for further studies targeting TBK1 as a potential treatment for inflammation-related diseases. Thus, optimizing and investigating highly selective cell-specific TBK1 inhibitors is important for their application in these diseases.

Acute respiratory tract infections pose a serious threat to the health of children worldwide, with viral infections representing a major etiology of this type of disease. Protective measures such as mask-wearing, social distancing, and hand hygiene can be effective in curbing the spread of severe acute respiratory syndrome coronavirus 2. These precautions may also have an impact on the spread of other respiratory viruses. In this study, we retrospectively compared the respiratory virus infections of children in Southwest China before and after the outbreak of COVID-19. Nasopharyngeal swabs were collected from 1578 patients under 14 years old with acute respiratory tract infection symptoms before and after COVID-19 pandemic. Nine common respiratory viruses including human bocavirus, human rhinoviruses, human coronaviruses, human adenoviruses, human metapneumovirus, respiratory syncytial virus, influenza A virus, influenza B virus, and parainfluenza virus were measured by advanced fragment analysis. The respiratory virus infection rates among children of all ages and genders in Southwest China under the precautions against COVID-19 pandemic were significantly lower than that of the same period before the pandemic. Our findings indicate that public health measures implemented during the COVID-19 pandemic, including strict mask-wearing, social distancing, and hand hygiene, may be effective in preventing the transmission of other respiratory viruses in children, thereby controlling the spread of infections.

Introduction: CXCL13 regulates the homing of lymphocytes. It is highly expressed in kidney and serum of SLE patients, and correlates with disease activity, but its value in LN is unclear. This study was to investigate the expression and diagnostic value of CXCL13 and its regulated CXCR5⁺ T cells in LN.Methods: In mice, the association of serum CXCL13 levels with renal function was analyzed. And CXCR5⁺ T cell was detected by H&E staining and immunofluorescence in kidney, and by flow cytometry in spleen. In clinical studies, the association of CXCL13 and CXCR5⁺ T cells with disease activity was verified, and their diagnostic efficacy was assessed by ROC curves.Results: CXCL13 was elevated in both mouse and patients, and was positively correlated with disease severity. Serum CXCL13 had an AUC of 0.9287 in the diagnosis of SLE and 0.6244 in differential diagnosis of LN. And in MRL/lpr mice, CXCL13 was involved in the development of nephritis by promoting the recruitment of CXCR5⁺ T cells to the kidney. In the peripheral blood of LN patients, CXCR5⁺ T cells were significantly reduced. Combined detection of CXCR5⁺ T cell subsets resulted in an AUC of 0.9672 for the diagnosis of SLE and 0.7867 for the differential diagnosis of LN.Discussion: Serum CXCL13 has high accuracy in the diagnosis of SLE, and circulating CXCR5⁺ T cells may serve as a novel biomarker for the diagnosis of SLE and LN, which might complement the poor performance of serum CXCL13 in the diagnostic efficacy of LN.