CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice.

CD38 is a transmembrane glycoprotein expressed by T-cells. It has been reported that patients with systemic lupus erythematosus (SLE) showed increased CD38+CD25+ T-cells correlating with immune activation and clinical signs. Contrariwise, CD38 deficiency in murine models has shown enhanced autoimmunity development. Recent studies have suggested that CD38+ regulatory T-cells are more suppressive than CD38- regulatory T-cells. Thus, we have suggested that CD38 overexpression in SLE patients could play a role in regulating immune activation cells instead of enhancing it. This study found a correlation between CD38 with FoxP3 expression and immunosuppressive molecules (CD69, IL-10, CTLA-4, and PD-1) in T-cells from lupus-prone mice (B6.MRL-Faslpr/J). Additionally, B6.MRL-Faslpr/J mice showed a decreased proportion of CD38+ Treg cells regarding wild-type mice (WT). Furthermore, Regulatory T-Cells (Treg cells) from CD38-/- mice showed impairment in expressing immunosuppressive molecules and proliferation after stimulation through the T-cell receptor (TCR). Finally, we demonstrated an increased ratio of IFN-γ/IL-10 secretion in CD38-/- splenocytes stimulated with anti-CD3 compared with the WT. Altogether, our data suggest that CD38 represents an element in maintaining activated and proliferative Treg cells. Consequently, CD38 could have a crucial role in immune tolerance, preventing SLE development through Treg cells.

The Impact of Quality Improvement Measures in the Management of Asthma Patients in Juvenile Detention Facilities.

Asthma is a serious chronic lung disease with a significant economic burden. The population of the San Bernardino County Juvenile Detention and Assessment Centers have higher odds of asthma as compared to the general population. Research has shown that a significant number of patients with a prior history of asthma were misdiagnosed. A protocol using objective testing, along with the detailed patient's history, was successfully implemented to verify the diagnosis and guide more effective medical care. After the implementation of those steps, the prevalence of asthma was found to be lower with the new protocol, from 18.1% in the pre-protocol period to 11.2% in the post-protocol period. This decrease resulted in an associated reduction in both direct and indirect healthcare costs and more efficient medical care.

HIV Disease Progression: Overexpression of the Ectoenzyme CD38 as a Contributory Factor?

Despite abundant evidence associating CD38 overexpression and CD4 T cell depletion in HIV infection, no causal relation has been investigated. To address this issue, a series of mechanisms are proposed, supported by evidence from different fields, by which CD38 overexpression can facilitate CD4 T cell depletion in HIV infection. According to this model, increased catalytic activity of CD38 may reduce CD4 T cells' cytoplasmic nicotin-amide adenine dinucleotide (NAD), leading to a chronic Warburg effect. This will reduce mitochondrial function. Simultaneously, CD38's catalytic products ADPR and cADPR may be transported to the cytoplasm, where they can activate calcium channels and increase cytoplasmic Ca2+ concentrations, further altering mitochondrial integrity. These mechanisms will decrease the viability and regenerative capacity of CD4 T cells. These hypotheses can be tested experimentally, and might reveal novel therapeutic targets. Also see the video abstract here https://youtu.be/k1LTyiTKPKs.