Alloreactive memory CD4 T cells promote transplant rejection by engaging DCs to induce innate inflammation and CD8 T cell priming.

Alloreactive memory T cells have been implicated as central drivers of transplant rejection. Perplexingly, innate cytokines, such as IL-6, IL-1β, and IL-12, are also associated with rejection of organ transplants. However, the pathways of innate immune activation in allogeneic transplantation are unclear.

Effector memory T cells induce innate inflammation by triggering DNA damage and a non-canonical STING pathway in dendritic cells.

Cognate interaction between CD4 effector memory T (T) cells and dendritic cells (DCs) induces innate inflammatory cytokine production, resulting in detrimental autoimmune pathology and cytokine storms. While T cells use tumor necrosis factor (TNF) superfamily ligands to activate DCs, whether T cells prompt other DC-intrinsic changes that influence the innate inflammatory response has never been investigated. We report the surprising discovery that T cells trigger double-strand DNA breaks via mitochondrial reactive oxygen species (ROS) production in interacting DCs.

IEC-intrinsic IL-1R signaling holds dual roles in regulating intestinal homeostasis and inflammation.

Intestinal epithelial cells (IECs) constitute a critical first line of defense against microbes. While IECs are known to respond to various microbial signals, the precise upstream cues regulating diverse IEC responses are not clear. Here, we discover a dual role for IEC-intrinsic interleukin-1 receptor (IL-1R) signaling in regulating intestinal homeostasis and inflammation.

Effector memory CD4 T cells induce damaging innate inflammation and autoimmune pathology by engaging CD40 and TNFR on myeloid cells.

Cytokine storm and sterile inflammation are common features of T cell-mediated autoimmune diseases and T cell-targeted cancer immunotherapies. Although blocking individual cytokines can mitigate some pathology, the upstream mechanisms governing overabundant innate inflammatory cytokine production remain unknown. Here, we have identified a critical signaling node that is engaged by effector memory T cells (T) to mobilize a broad proinflammatory program in the innate immune system.

IRF8 and BATF3 interaction enhances the cDC1 specific Pfkfb3 gene expression.

Dendritic cells (DCs) play central role in innate as well as adaptive immune responses regulated by diverse DC subtypes that vary in terms of surface markers, transcriptional profile and functional responses. Generation of DC diversity from progenitor stage is tightly regulated by complex molecular inter-play between transcription factors. We earlier demonstrated that Batf3 and Id2 expression have a synergistic effect on the Irf8 directed classical cDC1 development.

IRF1 governs the differential interferon-stimulated gene responses in human monocytes and macrophages by regulating chromatin accessibility.

Myeloid lineage cells use TLRs to recognize and respond to diverse microbial ligands. Although unique transcription factors dictate the outcome of specific TLR signaling, whether lineage-specific differences exist to further modulate the quality of TLR-induced inflammation remains unclear. Comprehensive analysis of global gene transcription in human monocytes, monocyte-derived macrophages, and monocyte-derived dendritic cells stimulated with various TLR ligands identifies multiple lineage-specific, TLR-responsive gene programs.

RelB suppresses type I Interferon signaling in dendritic cells.

Type I Interferon (IFN) signaling plays a critical role in dendritic cell (DC) development and functions. Inhibition of hyper type I IFN signaling promotes cDC2 subtype development. Relb is essential to development of cDC2 subtype and here we analyzed its effect on type I IFN signaling in DCs.

Essential role of HCMV deubiquitinase in promoting oncogenesis by targeting anti-viral innate immune signaling pathways.

Cancer is a multifactorial disease and virus-mediated carcinogenesis is one of the crucial factors, which is poorly understood. Human cytomegalovirus (HCMV) is a herpesvirus and its components have been evidenced to be associated with cancer of different tissue origin. However, its role in cancer remains unknown.