Homeostasis — literally 'standing still' — describes the mechanisms by which all biological systems maintain stability. In the immune system, although we know much about responses to the 'extreme' situation of an acute infection, it is important to also understand how immune pathways operate in steady-state conditions. When they function correctly, these homeostatic immune responses are barely visible, but like a graceful swan, the surface calm belies much hidden activity, and the consequences of dysfunction are significant.

The Review articles in this Focus describe several physiological systems in which the immune system contributes to homeostasis. In the gut, intestinal epithelial cells co-ordinate an immunological environment that enables beneficial host–commensal relationships. During wound healing in the liver, macrophages and other immune cells control the fibrotic cascade to ensure a self-limiting response. In all tissues, regulatory T cells balance adaptive immune responses and are themselves under the control of homeostatic processes that ensure context-specific activity. Tissue homeostasis also depends on the clearance of apoptotic cells from the body by phagocytic immune cells.

Research Highlights

Innate lymphoid cells: Nutrients direct immune balance


Nature Reviews Immunology, 14, 133 (2014)

Vitamin A deficiency shifts the balance of innate lymphoid cell subsets in the gut.

Regulatory T cells: Human skin residency


Nature Reviews Immunology, 14, 136 (2014)

A unique population of memory TReg cells resides in healthy human skin.

Immune tolerance: Mind the gap


Nature Reviews Immunology, 14, 136 (2014)

Intestinal CX3CR1+ macrophages can transfer processed antigen to CD103+ DCs through gap junctions for the induction of oral tolerance.

In brief

Macrophages: Microglia maintain optimal synapse density | PDF (567 KB)

p401 | doi:10.1038/nri3635

Nature Reviews Immunology, 14, 138 (2014)

Cytokines: IFNγ as sun protection? | PDF (566 KB)

p401 | doi:10.1038/nri3636

Nature Reviews Immunology, 14, 138 (2014)

Neonatal immunity: Long-term benefits of keeping mum | PDF (566 KB)

p401 | doi:10.1038/nri3637

Nature Reviews Immunology, 14, 138 (2014)


Intestinal epithelial cells: regulators of barrier function and immune homeostasis

David Artis & Lance W Peterson


Nature Reviews Immunology 14, 141–153 (2014)

Intestinal epithelial cells (IECs) promote gut homeostasis by coordinating the segregation and regulation of commensal microorganisms and the host immune system. This Review highlights the diverse and multifaceted roles of IECs in barrier function, and in their regulation of innate and adaptive immune cell function and homeostasis in response to microbial colonization.

Homeostatic control of regulatory T cell diversity

Adrian Liston & Daniel H. D. Gray


Nature Reviews Immunology 14, 154–165 (2014)

Regulatory T (TReg) cells are crucial for maintaining immune homeostasis in the body, with recent data showing that distinct TReg cell subsets become specialized to function in different tissues. Here, Liston and Gray highlight the need to regulate the number and function of the TReg cells themselves, and they describe the dynamic processes that achieve this homeostasis and functional specialization of TReg cell subsets.

Apoptotic cell clearance: basic biology and therapeutic potential

Ivan K. H. Poon, Christopher D. Lucas, Adriano G. Rossi & Kodi S. Ravichandran


Nature Reviews Immunology 14, 166-180 (2014)

The removal of apoptotic cells by phagocytes is essential for the maintenance of tissue homeostasis and is usually immunologically silent. However, dysregulation of this process is associated with numerous inflammatory and autoimmune diseases, and thus the therapeutic manipulation of apoptotic cell clearance by phagocytes may be a means to treat these diseases.

Liver fibrosis and repair: immune regulation of wound-healing in a solid organ

Antonella Pellicoro, Prakash Ramachandran, John P Iredale & Jonathan A Fallowfield


Nature Reviews Immunology 14, 181–194 (2014)

The immune regulation of liver fibrosis (particularly the distinct and opposing roles of macrophage subsets) provides an informative model of the endogenous mechanisms that mediate the resolution of fibrosis and the restoration of tissue homeostasis.

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