Sequential Transcriptional Changes Dictate Safe and Effective Antigen-Specific Immunotherapy Optimization of dosing strategy is critical for effective modulation of pathogenic ​CD4+ T-cell activity. Investigators report that dose escalation is imperative for safe, subcutaneous delivery of the high self-antigen doses required for effective tolerance induction, and elicits anergic ​interleukin-10-secreting regulatory ​CD4+ T cells. [Nat Commun] Full Article | Press Release TSC1 Controls Macrophage Polarization to Prevent Inflammatory Disease Investigators show that tuberous sclerosis complex 1 (TSC1) is a critical regulator of M1 and M2 phenotypes of macrophages. Mice with myeloid-specific deletion of TSC1 exhibit enhanced M1 response and spontaneously develop M1-related inflammatory disorders. However, TSC1-deficient mice are highly resistant to M2-polarized allergic asthma. [Nat Commun] Abstract Interleukin-10+ Regulatory B Cells Arise within Antigen-Experienced CD40+ B Cells to Maintain Tolerance to Islet Autoantigens Scientists hypothesized that naturally occurring, interleukin-10-producing regulatory B cells maintain tolerance to islet autoantigens, and that hyperglycemic nonobese diabetic mice and type 1 diabetes patients lack these potent negative regulators. [Diabetes] Abstract IL-23 Activates Innate Lymphoid Cells to Promote Neonatal Intestinal Pathology Investigators show that interleukin (IL)-23 promotes conversion of embryonic intestinal Lin−IL-23R+Thy1+ cells into IL-22-producing Thy1+Sca-1hi group 3 innate lymphoid cells in vitro. [Mucosal Immunol] Abstract The BCL6 RD2 Domain Governs Commitment of Activated B Cells to Form Germinal Centers To understand how the Bcl6 transcriptional repressor functions in the immune system, scientists disrupted its RD2 repression domain in mice. Bcl6RD2MUT mice exhibited a complete loss of germinal center formation but retained normal extrafollicular responses. [Cell Rep] Full Article | Graphical Abstract IL-6 trans-Signaling-Dependent Rapid Development of Cytotoxic CD8+ T Cell Function During inflammation, mature antigen-presenting dendritic cells instruct naive T cells within lymphoid organs to develop into effector T cells. Researchers report a mechanistically distinct and more rapid process of effector T cell development occurring within 18 hours. Interleukin-6 (IL-6) trans-signaling was required and sufficient for rapid induction of granzyme B expression in CD8+ T cells. [Cell Rep] Full Article | Graphical Abstract | Press Release CD4+FoxP3+ Regulatory T Cells Suppress Fatal T Helper 2 Cell Immunity during Pulmonary Fungal Infection Researchers investigated the role of regulatory T (Treg) cells during experimental murine pulmonary Cryptococcus neoformans infection. In Treg cell-depleted mice, stronger pulmonary allergic inflammation with enhanced mucus production and pronounced eosinophilia, increased IgE production, and elevated fungal lung burden were found. This was accompanied by higher frequencies of GATA-3+ T helper 2 cells with elevated capacity to produce interleukin (IL)-4, IL-5 and IL-13. [Eur J Immunol] Abstract Activation of CD1d-Restricted Natural Killer T Cells Can Inhibit Cancer Cell Proliferation during Chemotherapy by Promoting the Immune Responses in Murine Mesothelioma Investigators studied the impact of natural killer T (NKT) cell activation by alpha-galactosylceramide (α-GC) on cancer cell repopulation during chemotherapy in murine mesothelioma. NKT cells specifically recognized α-GC through CD1d resulting in their activation and expansion. [Cancer Immunol Immunother] Abstract Subscribe to our sister publications: Human Immunology News and Immunology of Infectious Disease News! |