Citations

Abstract Stearoyl‐CoA desaturases (SCD) are endoplasmic reticulum (ER)‐associated enzymes that catalyze the synthesis of the monounsaturated fatty acids (MUFAs). As such, SCD play important roles in maintaining the intracellular balance between saturated fatty acid (SFAs) and MUFAs. The roles of SCD in CD4 + T‐helper cell responses are currently unexplored. Here, we have found that murine and human follicular helper T (T FH ) cells express higher levels of SCD compared to non‐T FH cells. Further, the expression of SCD in T FH cells is dependent on the T FH lineage‐specification transcription factor BCL6. We found that the inhibition of SCD impaired T FH cell maintenance and shifted the balance between T FH and follicular regulatory T (T FR ) cells in the spleen. Consequently, SCD inhibition dampened germinal center B‐cell responses following influenza immunization. Mechanistically, we found that SCD inhibition led to increased ER stress and enhanced T FH cell apoptosis in vitro and in vivo. These results reveal a possible link between fatty acid metabolism and cellular and humoral responses induced by immunization or potentially, autoimmunity.

Background: The sex- and gender-specific health (SGSH) multimedia case-based learning modules (MCBLMs) were developed to address the absence of validated or peer-reviewed material that incorporates topics of sex and gender differences into medical curricula. This article provides the methodology for development of the modules and reports the results of a field test of the modules in different medical educational settings. Methods: MCBLMs were created by a multidisciplinary committee of scientists, health profession educators, and students. Two modules, osteoporosis and diabetes, were tested in various settings based on the curricular needs at each of the five accredited institutions. Each module consisted of a pretest and three interactive, multimedia stand-alone sections with post-tests. Scores on the tests were compared using a paired-samples t -test. A postmodule survey was used to evaluate the format. Results: Four hundred eighteen students participated in the field testing. For the 194 who completed the osteoporosis module, the post-test scores (M = 13.71, standard deviation [SD] = 2.09) were significantly higher than the pretest scores (M = 10.54, SD = 2.41), p < 0.001. Post-test scores for the 285 who completed the diabetes module (M = 16.55, SD = 2.46) were also significantly higher than the pretest scores (M = 13.71, SD = 2.09), p < 0.001. The postmodule survey showed positive acceptance of the format with an average score of 3.54/4 for osteoporosis and 3.45/4 for diabetes. Conclusion: The SGSH MCBLM field testing results show that the modules have a positive effect on content knowledge in multiple settings and are well accepted by learners.

Exhausted-like CD8 + resident memory T cells in the lung limit immune activation–driven fibrosis.

Respiratory viral infections, like IAV and respiratory syncytial virus (RSV) infections, impose great challenges to public health. Alveolar macrophages (AM) are lung-resident immune cells that play important roles in protecting the host against IAV and RSV infections. However, the underlying molecular mechanisms by which AM modulate host inflammation, disease development, and tissue recovery are not very well understood. Here we identify that PPAR-γ expression in AM is crucial to suppress pulmonary inflammation and diseases and to promote fast host recovery from IAV and RSV infections. Our data suggest that targeting macrophage PPAR-γ may be a promising therapeutic option in the future to suppress acute inflammation and simultaneously promote recovery from severe diseases associated with respiratory viral infections.

Abstract Follicular Th (Tfh) cells are a distinct subset of Th cells that help B cells produce class-switched antibodies. Studies have demonstrated that Tfh cells are highly prone to HIV infection and replication. However, the molecular mechanisms underlying this phenomenon are largely unclear. Here, we show that murine and human Tfh cells have diminished constitutive expression of IFN-stimulated genes (ISGs) inclusive of antiviral resistance factor MX dynamin-like GTPase 2 (MX2) and IFN-induced transmembrane 3 (IFITM3) compared with non-Tfh cells. A lower antiviral resistance in Tfh was consistent with a higher susceptibility to retroviral infections. Mechanistically, we found that BCL6, a master regulator of Tfh cell development, binds to ISG loci and inhibits the expression of MX2 and IFITM3 in Tfh cells. We demonstrate further that inhibition of the BCL6 BR-C, ttk, and bab (BTB) domain function increases the expression of ISGs and suppresses HIV infection and replication in Tfh cells. Our data reveal a regulatory role of BCL6 in inhibiting antiviral resistance factors in Tfh cells, thereby promoting the susceptibility Tfh cells to viral infections. Our results indicate that the modulation of BCL6 function in Tfh cells could be a potential strategy to enhance Tfh cell resistance to retroviral infections and potentially decrease cellular reservoirs of HIV infection.