Cardiovascular disease is the leading cause of mortality worldwide, and atherosclerosis the principal factor underlying cardiovascular events. Atherosclerosis is a chronic inflammatory disease characterized by endothelial dysfunction, intimal lipid deposition, smooth muscle cell proliferation, cell apoptosis and necrosis, and local and systemic inflammation, involving key contributions to from innate and adaptive immunity. The balance between proatherogenic inflammatory and atheroprotective anti-inflammatory responses is modulated by a complex network of interactions among vascular components and immune cells, including monocytes, macrophages, dendritic cells, and T, B, and foam cells; these interactions modulate the further progression and stability of the atherosclerotic lesion. In this review, we take a global perspective on existing knowledge about the pathogenesis of immune responses in the atherosclerotic microenvironment and the interplay between the major innate and adaptive immune factors in atherosclerosis. Studies such as this are the basis for the development of new therapies against atherosclerosis. Int. J. Mol. Sci. 2019, 20, 5293 2 of 48 cytotoxic T lymphocytes at the interface between innate and adaptive immunity. Abundant evidence indicates that innate and adaptive immunity both play important roles in the onset and progression of atherosclerosis [1][2][3]. For example, Csf1 −/− mice, which lack macrophage colony stimulating factor (M-CSF, also known as CSF1) are less prone to developing atherosclerosis [4]. Moreover, mice lacking B and T cells (Rag1 −/− or Rag2 −/− mice lacking recombination-activating genes 1 or 2 or mice carrying the severe combined immunodeficiency (SCID) mutation) are resistant to atherosclerosis in the presence of mild hypercholesterolemia [5][6][7][8][9][10]. Int. J. Mol. Sci. 2019, 20, 5293 2 of 46 cells are cytotoxic T lymphocytes at the interface between innate and adaptive immunity. Abundant evidence indicates that innate and adaptive immunity both play important roles in the onset and progression of atherosclerosis [1][2][3]. For example, Csf1 −/− mice, which lack macrophage colony stimulating factor (M-CSF, also known as CSF1) are less prone to developing atherosclerosis [4]. Moreover, mice lacking B and T cells (Rag1 −/− or Rag2 −/− mice lacking recombination-activating genes 1 or 2 or mice carrying the severe combined immunodeficiency (SCID) mutation) are resistant to atherosclerosis in the presence of mild hypercholesterolemia [5-10]. Atherosclerosis's PathophysiologyAtherosclerosis is a chronic inflammatory disease of large and medium-sized arteries [20], characterized by endothelial dysfunction and the accumulation of low-density lipoproteins (LDL), immune cells, and necrotic debris in the subendothelial space, resulting in the formation of an atherosclerotic plaque [21][22][23][24]. LDL deposition is more likely in regions with turbulent flow and low shear stress [25] sensed by the vascular endothelium [26]. Turbulent flow modulates endothelial transcrip...

Inflammatory bowel disease (IBD) is a heterogeneous state of chronic intestinal inflammation of unknown cause encompassing Crohn’s disease (CD) and ulcerative colitis (UC). IBD has been linked to genetic and environmental factors, microbiota dysbiosis, exacerbated innate and adaptive immunity and epithelial intestinal barrier dysfunction. IBD is classically associated with gut accumulation of proinflammatory Th1 and Th17 cells accompanied by insufficient Treg numbers and Tr1 immune suppression. Inflammatory T cells guide innate cells to perpetuate a constant hypersensitivity to microbial antigens, tissue injury and chronic intestinal inflammation. Recent studies of intestinal mucosal homeostasis and IBD suggest involvement of innate lymphoid cells (ILCs). These lymphoid-origin cells are innate counterparts of T cells but lack the antigen receptors expressed on B and T cells. ILCs play important roles in the first line of antimicrobial defense and contribute to organ development, tissue protection and regeneration, and mucosal homeostasis by maintaining the balance between antipathogen immunity and commensal tolerance. Intestinal homeostasis requires strict regulation of the quantity and activity of local ILC subpopulations. Recent studies demonstrated that changes to ILCs during IBD contribute to disease development. A better understanding of ILC behavior in gastrointestinal homeostasis and inflammation will provide valuable insights into new approaches to IBD treatment. This review summarizes recent research into ILCs in intestinal homeostasis and the latest advances in the understanding of the role of ILCs in IBD, with particular emphasis on the interaction between microbiota and ILC populations and functions.

Inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), is a heterogeneous state of chronic intestinal inflammation with no exact known cause. Intestinal innate immunity is enacted by neutrophils, monocytes, macrophages, and dendritic cells (DCs), and innate lymphoid cells and NK cells, characterized by their capacity to produce a rapid and nonspecific reaction as a first-line response. Innate immune cells (IIC) defend against pathogens and excessive entry of intestinal microorganisms, while preserving immune tolerance to resident intestinal microbiota. Changes to this equilibrium are linked to intestinal inflammation in the gut and IBD. IICs mediate host defense responses, inflammation, and tissue healing by producing cytokines and chemokines, activating the complement cascade and phagocytosis, or presenting antigens to activate the adaptive immune response. IICs exert important functions that promote or ameliorate the cellular and molecular mechanisms that underlie and sustain IBD. A comprehensive understanding of the mechanisms underlying these clinical manifestations will be important for developing therapies targeting the innate immune system in IBD patients. This review examines the complex roles of and interactions among IICs, and their interactions with other immune and non-immune cells in homeostasis and pathological conditions.