Correlation between circulating innate lymphoid cell precursors and thymic function
Sandra Bajana,
Aneta Pankow,
Kaili Liu,
Martyna Michniowska,
Joseph F. Urban, Jr.,
Wei R. Chen,
Xiao-Hong Sun
Affiliations
Sandra Bajana
Oklahoma Medical Research Foundation, Program in Arthritis and Clinical Immunology, 825 NE 13thStreet, Oklahoma City, OK 73104, USA
Aneta Pankow
Oklahoma Medical Research Foundation, Program in Arthritis and Clinical Immunology, 825 NE 13thStreet, Oklahoma City, OK 73104, USA
Kaili Liu
Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73104, USA
Martyna Michniowska
Oklahoma Medical Research Foundation, Program in Arthritis and Clinical Immunology, 825 NE 13thStreet, Oklahoma City, OK 73104, USA
Joseph F. Urban, Jr.
United States Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, MD 73104, USA
Wei R. Chen
Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73104, USA
Xiao-Hong Sun
Oklahoma Medical Research Foundation, Program in Arthritis and Clinical Immunology, 825 NE 13thStreet, Oklahoma City, OK 73104, USA; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Corresponding author
Summary: The thymus has a high capacity to support the differentiation of ILCs, especially when E protein transcription factors are ablated. Whether it contributes to the homeostasis of ILC pools in tissues is not clear. Single-cell RNA sequencing analysis shows a substantial amount of ILC precursors in wild type but not athymic nude blood. The precursors express CD3 intracellularly (ic) but not on the surface. The abundance of Lin−CD127+CD62L+icCD3ε+ precursors varies with age, peaking at 2–3 months. These cells can differentiate into various ILC subsets on OP9-DL1 stroma in vitro. In the lung, small intestine, and epidermis, icCD3ε+ cells differentiate into diverse ILC subsets in different tissue environments in steady state. Helminth infection promotes their differentiation toward functional ILC2s. Thus, the thymus appears to play a role in replenishing ILC pools in different peripheral tissues. Because thymic activity is age-dependent, this finding may help explain age-related differences in immune responses.
