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CD45RA(+)CD62L(-) ILCs in human tissues represent a quiescent local reservoir for the generation of differentiated ILCs
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- Kokkinou, Efthymia (author)
- Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
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- Pandey, Ram Vinay (author)
- Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Karolinska Inst, Dept Med, Stockholm, Sweden.
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- Mazzurana, Luca (author)
- Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden.
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- Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Karolinska Inst, Dept Med, Stockholm, Sweden. (creator_code:org_t)
- AMER ASSOC ADVANCEMENT SCIENCE, 2022
- 2022
- English.
- In: Science immunology. - : AMER ASSOC ADVANCEMENT SCIENCE. - 2470-9468. ; 7:70
- Journal article (peer-reviewed)
Abstract
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- Innate lymphoid cells (ILCs) are highly plastic and predominantly mucosal tissue-resident cells that contribute to both homeostasis and inflammation depending on the microenvironment. The discovery of naive-like ILCs suggests an ILC differentiation process that is akin to naive T cell differentiation. Delineating the mechanisms that underlie ILC differentiation in tissues is crucial for understanding ILC biology in health and disease. Here, we showed that tonsillar ILCs expressing CD45RA lacked proliferative activity, indicative of cellular quiescence. CD62L distinguished two subsets of CD45RA(+) ILCs. CD45RA(+)CD62L(+) ILCs (CD62L(+) ILCs) resembled circulating naive ILCs because they lacked the transcriptional, metabolic, epigenetic, and cytokine production signatures of differentiated ILCs. CD45RA(+)CD62L(-) ILCs (CD62L(-) ILCs) were epigenetically similar to CD62L(+) ILCs but showed a transcriptional, metabolic, and cytokine production signature that was more akin to differentiated ILCs. CD62L(+) and CD62L(-) ILCs contained uni- and multipotent precursors of ILC1s/NK cells and ILC3s. Differentiation of CD62L(+) and CD62L(-) ILCs led to metabolic reprogramming including up-regulation of genes associated with glycolysis, which was needed for their effector functions after differentiation. CD62L(-) ILCs with preferential differentiation capacity toward IL-22-producing ILC3s accumulated in the inflamed mucosa of patients with inflammatory bowel disease. These data suggested distinct differentiation potential of CD62L(+) and CD62L(-) ILCs between tissue microenvironments and identified that manipulation of these cells is a possible approach to restore tissue-immune homeostasis.
Subject headings
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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