Tissue-Resident ILC2s Across Organs - Review Article - Heterogeneity, Niche Crosstalk, and Shared Regulatory Circuits

Sep 30, 2026

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Type 2 innate lymphoid cells (ILC2s) act as a key source of innate cytokines that promote allergic inflammation. Increasing evidence indicates that ILC2s also function in peripheral tissues including lung, fat, intestine, and skin, driven by alarmins, neuropeptides, and environmental cues. Additional findings show ILC2s in pancreas, uterus, and meninges, supporting normal physiology. This review summarizes recent work on ILC2 physiological roles across multiple tissues, highlighting their importance in type 2 immunity and tissue homeostasis.

LanguageEnglish

CategoryHealthcare

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Pages24

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Introduction

Biological Role of ILC2s in Peripheral Tissues

Abbreviations

Conflict of Interest

Author Contributions

Immune Netw. 2025 Dec;25(6):e40 [https://doi.org/10.4110/in.2025.25.e40](https://doi.org/10.4110/in.2025.25.e40)[ ](https://doi.org/10.4110/in.2025.25.e40)pISSN 1598-2629·eISSN 2092-6685 Review Article Received: Jul 30, 2025 Revised: Oct 20, 2025 Accepted: Oct 23, 2025 Published online: Dec 1, 2025 *Correspondence to Steven J. Van Dyken Department of Pathology & Immunology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA. Email: [svandyken@wustl.edu](svandyken@wustl.edu) Do-Hyun Kim Department of Life Science, College of Natural Sciences, Hanyang University, 222 Wangsimniro, Seongdong-gu, Seoul 04763, Korea. Email: [dohkim@hanyang.ac.kr](dohkim@hanyang.ac.kr) †Haksung Kim, Jangho Lim, and Jongmin Baek contributed equally to this work. Copyright © 2025. The Korean Association of Immunologists This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([https://](https://)[ ](https://)[creativecommons.org/licenses/by-nc/4.0/](creativecommons.org/licenses/by-nc/4.0/)) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ORCID iDs Haksung Kim [https://orcid.org/0009-0006-7363-9659](https://orcid.org/0009-0006-7363-9659)[ ](https://orcid.org/0009-0006-7363-9659)Jangho Lim [https://orcid.org/0009-0004-0539-7999](https://orcid.org/0009-0004-0539-7999)[ ](https://orcid.org/0009-0004-0539-7999)Jongmin Baek [https://orcid.org/0009-0003-1068-6683](https://orcid.org/0009-0003-1068-6683)[ ](https://orcid.org/0009-0003-1068-6683)[Steven J. Van Dyken](Steven J. Van Dyken) [https://orcid.org/0000-0002-9787-0883](https://orcid.org/0000-0002-9787-0883) Tissue-Resident ILC2s Across Organs: Heterogeneity, Niche Crosstalk, and Shared Regulatory Circuits Haksung Kim 1,†, Jangho Lim 1,†, Jongmin Baek 1,†, Steven J. Van Dyken 2,*, Do-Hyun Kim 1,3,4,5,* 1Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Korea 2Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA 3Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul 04763, Korea 4Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea 5Research Institute for Convergence of Basic Sciences, Hanyang University, Seoul 04763, Korea ABSTRACT Type 2 innate lymphoid cells (ILC2s) are an important source of innate cytokines that contribute to allergic inflammation. Recent studies have also suggested that ILC2s playa biological role in peripheral tissues such as lung, fat, intestine and skin, controlled by alarmins, neuropeptides and environmental factors. Furthermore, emerging studies have shown that tissues including the pancreas, uterus and meninges contain ILC2s that contribute to normal biological function. Here, we review recent studies on the physiological function of ILC2s in multiple tissues, emphasizing their importance not only in type 2 immune responses, but also in maintaining biological homeostasis. Keywords: ILC2; Tissue homeostasis; Alarmin; Biological function INTRODUCTION Like individuals in our society, the cells in our body interact with each other. Some cells give guidance to others, while some inhibit other’s function, and these interactions, together, form a highly complex and intimate network that regulates biological function. During development, precursor cells differentiate into mature cells with unique functions, and these cells are inevitably involved in tissue niches, working in close concert with other cells in the tissue microenvironment. Thus, tissue-specific niches ultimately dictate the fate of precursor cells. Tissue-resident immune cells are located in peripheral tissues and have specific functions depending on their localization (1,2). Their primary roles are to protect the host from infection and

FAQs

What are tissue-resident ILC2s known for in immune responses?

Tissue-resident ILC2s are important sources of innate cytokines that contribute to allergic inflammation, reflecting their central role in type 2 immune responses.

Which peripheral tissues contain ILC2s according to the review?

The review highlights ILC2 presence in lung, fat, intestine, and skin, and also notes tissues such as pancreas, uterus, and meninges where ILC2s contribute to normal biological function.

What factors are described as controlling ILC2 activity in tissues?

ILC2s are described as being controlled by alarmins, neuropeptides, and environmental factors that shape their tissue-specific behavior.

Sep 30, 2026

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