Galectin-9 is a risk gene in inflammatory bowel disease. By transcriptomic analyses of ileal biopsies and PBMCs from inflammatory bowel disease patients, we identified a positive correlation between galectin-9 expression and colitis severity. We observed that galectin-9–deficient T cells were less able to induce T cell–mediated colitis. However, several mouse-based studies reported that galectin-9 treatment induces T cell apoptosis and ameliorates autoimmune diseases in an exogenously modulated manner, indicating a complicated regulation of galectin-9 in T cells. We found that galectin-9 is expressed mainly inside T cells, and its secreted form is barely detected under physiological conditions. Endogenous galectin-9 was recruited to immune synapses upon T cell activation. Moreover, proximal TCR signaling was impaired in galectin-9–deficient T cells, and proliferation of these cells was decreased through an intracellularly modulated manner. Th17 cell differentiation was downregulated in galectin-9–deficient T cells, and this impairment can be rescued by strong TCR signaling. Taken together, these findings suggest that intracellular galectin-9 is a positive regulator of T cell activation and modulates the pathogenesis of autoimmune diseases.

Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HAmg) produced cross-strain-reactive antibodies and were better protected than mice injected with a fully glycosylated HA (HAfg) during lethal dose challenge. We employed a single B-cell screening platform to isolate the cross-protective monoclonal antibody (mAb) 651 from mice immunized with the HAmg of A/Brisbane/59/2007 (H1N1) influenza virus (Bris/07). The mAb 651 recognized the head domain of a broad spectrum of HAs from groups 1 and 2 influenza A viruses and offered prophylactic and therapeutic efficacy against A/California/07/2009 (H1N1) (Cal/09) and Bris/07 infections in mice. The antibody did not possess neutralizing activity; however, antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis mediated by natural killer cells and alveolar macrophages were important in the protective efficacy of mAb 651. Together, this study highlighted the significance of effector functions for non-neutralizing antibodies to exhibit protection against influenza virus infection.

Blimp-1, encoded by Prdm1, is a master transcriptional factor that governs the differentiation fate of many cell types, including epidermal keratinocytes. Previous results from our laboratory showed that inducible deletion of Prdm1 in mouse epidermis spontaneously induces skin inflammation. Epidermis composes of not only epidermal keratinocytes, but also epidermal appendages, including hair follicles, sebaceous glands and sweat glands. Sebaceous glands release the “oil” contents that lubricate the skin. Our previous results also showed that Blimp-1 is required for the maintenance of the homeostasis of terminally differentiated sebocytes. Here, we aim to investigate the potential function of Blimp-1 in inflammation and lipid metabolism in sebocytes. We depleted Blimp-1 by siRNA in SZ95, the immortalized human sebocyte cells. We found accumulated and enlarged lipid droplets in Blimp-1 depleted cells. Consistently, gas chromatography–mass spectrometry (GC-MS) analyses showed that the levels of several long-chain fatty acids, including 1,3-dipalmitoyl-2oleoylglycerol, 1-palmitoyl-2oleoyl-3-lineoleoyl-rac-glycerol, and triolein, were accumulated in Blimp-1-depleted SZ95 cells, linking with the significant increases in the production of pro-inflammatory cytokines, including IL-1β, IL-6, IL-8 and IL-18. Thus, Blimp-1 served as a pivotal mediator in the regulation of the inflammatory responses in epidermis, likely also through affecting the lipid metabolism and cytokine production in sebocytes.