Research Topic

Circuits of Resident Immunity Regulating Tissue Adaptation and Organ Homeostasis

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Immune cells establish tissue-residency in almost every peripheral organ to facilitate immunity. However, specialized structures, such as primary, secondary or tertiary lymphoid organs, are often required for optimal activation and maturation of immune cells, prior to settling in peripheral organs. While the ...

Immune cells establish tissue-residency in almost every peripheral organ to facilitate immunity. However, specialized structures, such as primary, secondary or tertiary lymphoid organs, are often required for optimal activation and maturation of immune cells, prior to settling in peripheral organs. While the activation and maturation of immune cells are required for imprinting organ-homing specificity, tissue-resident cells, in particular immune cells, adopt transcriptional and epigenetic trajectories that are characteristic for the organ that they migrate to. Unique microenvironments within peripheral organs are believed to support the adaptation of tissue-resident cells to their new home.

Among tissue-resident immune cells, innate lymphoid cells (ILCs), macrophages, monocytes, in addition to lymphocytes, such as subsets of tissue-resident T cells and antibody-secreting plasma cells, have emerged as important regulators of local homeostasis, whereby they remain inside their resident tissues and locally undergo renewal. Tissue-resident immune cells fulfill pivotal functions including (i) orchestrating local immunity, (ii) regulating organ function, and ultimately, (iii) maintaining whole body homeostasis. Experimental evidence supporting the importance of tissue-resident immune cells has been demonstrated in a diverse array of tissues. These examples include: (i) the interaction of lymphoid tissue-inducer (LTi) cells and stromal cells which defines the formation of secondary lymphoid organs; (ii) the role of glial cells in the maintenance of the nervous system; (iii) the roles of group 3 ILCs and γδ T cells in maintaining epithelial barrier functions and (iv) the importance of group 2 ILCs and regulatory T cells in the regulation of metabolic homeostasis.

The requirement to fulfill a diverse range of tissue regulatory functions has evolutionarily shaped the crosstalk and interactions between tissue-resident and non-hematopoietic entities, such as parenchymal cells, epithelial cells, neurons, stromal cells and adipocytes. As a result, the interplay between hematopoietic and non-hematopoietic cells is indispensable for organ development and function, thus integrating the functional specialization of immune cells in their resident tissues. Although recent research has helped us gain insight into the mechanisms underlying tissue-resident immunity, there is a huge gap in our knowledge of how the interactions between tissue-resident immune cells and non-hematopoietic cells regulate organ and body homeostasis in health and disease. This Research Topic aims to summarize, and foster to further research efforts, in the field of tissue-resident immune regulation.

In this Research Topic, we welcome the submission of Original Research articles and Review articles on various tissue-resident immune cell populations with a particular focus on ILC subsets, γδ T cells and unconventional T cells, dendritic cells, macrophages and monocytes. We welcome submissions that include, but are not limited, to the following sub-topics:

1. Crosstalk between tissue-resident immune cells and parenchymal cells.
2. Pathophysiology of tissue-resident circuits involving adaptive and innate immune cells.
3. Tissue-specific cues involving resident immune cells and the signal transduction pathways modulated by these cues.
4. Development, maturation and migration of tissue-resident innate and adaptive immune cells.
5. Regulation of organ development by tissue-resident innate and adaptive immune cells.
6. Non-immunological functions of tissue-resident immune cells including wound healing, tissue remodelling, and the regulation of metabolic homeostasis.
7. Transcriptional and epigenetic imprinting of tissue-resident immune cells.
8. Metabolic adaptation of tissue-resident innate and adaptive immune cells.
9. Induction and maintenance of memory in tissue-resident immune cells.


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