Abstract
Group 2 innate lymphoid cells (ILC2s) are a member of the ILC family and are involved in protective and pathogenic type 2 responses. Recent research has highlighted their involvement in modulating tissue and immune homeostasis during health and disease and has uncovered critical signaling circuits. While interactions of ILC2s with the bacterial microbiome are rather sparse, other microbial members of our microbiome, including helminths and protozoans, reveal new and exciting mechanisms of tissue regulation by ILC2s. Here we summarize the current field on ILC2 activation by the tissue and immune environment and highlight particularly new intriguing pathways of ILC2 regulation by protozoan commensals in the intestinal tract.
Highlights
Research over the last decade has redirected focus away from classical immune cell interactions within lymphoid tissues towards immunity within non-lymphoid tissues
The commitment towards the innate lymphoid cells (ILCs) lineages happens at the early innate lymphoid progenitor (EILP) stage, while diversification of ILCs, dictated by lineage-defining transcription factors, appears in the common innate lymphocyte progenitor (CILP) that restricts their potential to only generate group 1-3 ILCs and natural killer (NK) cells
Differentiation of ILC2 precursors (ILC2p) into immature ILC2 and mature ILC2 is mediated by upstream cytokines such as IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) secreted by epithelial cells and myeloid cells [13]
Summary
Research over the last decade has redirected focus away from classical immune cell interactions within lymphoid tissues towards immunity within non-lymphoid tissues. The identification of tissue-resident lymphoid cells lacking B and T cell markers while retaining the expression of common-gamma chain (CD132)-associated receptors for IL-7, IL-15, or TSLP (i.e., CD127/IL-7Ra, CD122/IL-2Rb, and cytokine receptor-like factor/Crlf2/TSLPR) revealed the presence of innate lymphoid cells (ILCs) in almost every solid organ [3]. These lymphocytes rapidly secrete cytokines upon stimulation and facilitate early/immediate responses against local changes in the tissue environment [4,5]. We will close this review by focusing on new, emerging microbial members of the intestinal microbiome and their implication in regulating ILC2 functions [7]
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