Microbiota in T-cell homeostasis and inflammatory diseases

Abstract

The etiology of disease pathogenesis can be largely explained by genetic variations and several types of environmental factors. In genetically disease-susceptible individuals, subsequent environmental triggers may induce disease development. The human body is colonized by complex commensal microbes that have co-evolved with the host immune system. With the adaptation to modern lifestyles, its composition has changed depending on host genetics, changes in diet, overuse of antibiotics against infection and elimination of natural enemies through the strengthening of sanitation. In particular, commensal microbiota is necessary in the development, induction and function of T cells to maintain host immune homeostasis. Alterations in the compositional diversity and abundance levels of microbiota, known as dysbiosis, can trigger several types of autoimmune and inflammatory diseases through the imbalance of T-cell subpopulations, such as Th1, Th2, Th17 and Treg cells. Recently, emerging evidence has identified that dysbiosis is involved in the progression of rheumatoid arthritis, type 1 and 2 diabetic mellitus, and asthma, together with dysregulated T-cell subpopulations. In this review, we will focus on understanding the complicated microbiota-T-cell axis between homeostatic and pathogenic conditions and elucidate important insights for the development of novel targets for disease therapy.

Figure 1

Microbiota diversity is determined by environmental factors and signals to distal organs that contribute the development of diseases. The microbiota is established by other environmental factors, such as dietary fiber, saturated lipids, infection and antibiotics, and its colonization depends on the physiological condition of each tissue. Altered commensal microbiota in the gut or lung could influence the progression of various tissue-specific diseases through signal mediators, including microbes, microbial metabolites and circulating immune cells.

Figure 2

Microbiota mediates T-cell differentiation in homeostatic or pathogenic conditions. In mice under germ-free (GF) conditions, Bacteroides fragilis restores the development of the Th1-associated immune response through a bacterial product, polysaccharide A (PSA)-dependent pathway, while in mice under specific pathogen-free (SPF) conditions, PSA derived from B. fragilis induces Treg cell accumulation. Segmented filamentous bacteria (SFB) induces a Th17 immune response through adenosine 5′-triphosphate (ATP) production or serum amyloid A (SAA) produced by innate cells. Clostridium sp. promotes Treg cells through short-chain fatty acid (SCFA) production. Antigen-presenting cells (APCs) activated by cognate bacterial antigens could facilitate the generation of tissue-specific T cells derived from systemic T cells in a specific tissue environment.