Analysis of the Evolutionary Path and Hotspots of Innate Lymphoid Cells Based on a Knowledge Map
Innate lymphoid cells (ILCs) represent a heterogeneous population of lymphocytes that lack specific antigen receptors but produce effective cytokines to match T helper cell subsets. Over the past decade, research on ILCs has revealed their critical roles as tissue-resident cells involved in regulating tissue inflammation, tissue remodeling, and metabolic homeostasis. These cells are implicated in various diseases, including asthma, allergic rhinitis, inflammatory bowel disease, and cancer. While numerous publications have summarized research in this field, most have been descriptive literature reviews or qualitative taxonomic studies, which fail to fully and objectively reflect the comprehensive landscape of ILC research. This study aims to evaluate the development of ILC research and explore its future prospects by examining the evolutionary path of research hotspots, as well as the temporal and geographic distribution of studies in this field.
Bibliometrics, a method that employs knowledge map tools such as CiteSpace, Histcite, and VOSviewer, was utilized to reveal research hotspots and predict future trends. In this study, a knowledge map analysis was conducted on ILC-related studies published between 2010 and 2019 using CiteSpace V 5.0.R1 SC. Data were extracted from the Science Citation Index Expanded database of the Web of Science Core Collection on August 3, 2019. The search terms included “innate lymphoid cells,” “natural helper cells,” “nuocytes,” “innate type 2 helper,” “multipotent progenitor type 2,” “IH2 cells,” “mpptype2,” “natural killer 22 cells,” and “natural cytotoxicity receptor 22 cells.” These terms were chosen to account for the various nomenclatures used for ILCs since their classification was proposed in 2013. The timespan was set from 2010 to 2019, and the document types were restricted to “articles” and “reviews.” The search yielded 3083 papers that met the inclusion criteria.
From 2010 to 2019, 3083 documents related to ILC research were published, demonstrating a significant increase in output, from 12 papers in 2010 to 660 in 2018. The research on ILCs accelerated notably after 2014, with 2784 papers published between 2014 and 2019, accounting for approximately 90.3% of the total publications over the decade. This rapid growth indicates the increasing interest and importance of ILC research in the scientific community.
The co-author network knowledge map for ILC research illustrates the collaborative relationships among researchers in this emerging field. Andrew N.J. McKenzie leads with 58 articles, followed by David Artis (52 papers), Marco Colonna (37 papers), and Eric Vivier (34 papers). The map reveals various collaborative groups of different sizes, most of which are interconnected but not closely linked. This suggests that while there is some level of collaboration, academic exchange and research cooperation in the field of ILCs could be further enhanced.
The spatial distribution of ILC research highlights the number of published papers, the extent of international cooperation, and the centrality of top countries and institutions. Three primary clusters dominate the field: the United States, France, and China. Based on the number of publications, the United States (1333 articles), the United Kingdom (367 articles), and China (332 articles) are the leading contributors, accounting for 65.9% of the total publications. Other significant contributors include Germany, Japan, and France. Among institutions, Institut Pasteur ranks first with 92 papers, followed by Washington University, the National Institute of Allergy and Infectious Diseases, and Harvard Medical School. The Chinese Academy of Science ranks 33rd with 26 papers. Many institutions in the United States have established cooperative relationships with other countries, reflecting the strong research potential and academic exchange awareness in the field of ILCs. This collaborative environment likely contributes to the high research output of the United States.
The timeline map of hot keywords in ILC research over the past decade reveals three primary clusters: “immunity related,” “cell biology related,” and “disease related.” In the immunity-related cluster, the most frequent keywords include adaptive immunity (168 mentions), type 2 immunity (223 mentions), immune response (174 mentions), dendritic cells (469 mentions), and T cells (427 mentions). In the cell biology cluster, the top keywords are natural killer cells (594 mentions), ror gamma t (323 mentions), cytokines (338 mentions), and differentiation (315 mentions). The disease-related cluster features keywords such as inflammation (574 mentions), asthma (379 mentions), inflammatory bowel disease (178 mentions), homeostasis (144 mentions), and cancer (66 mentions).
In the early stages of ILC research (before 2014), the most popular keywords were allergic airway inflammation, homeostasis, atopic dermatitis, adipose tissue, adaptive immunity, T helper cells, cytokines, and dendritic cells. These topics remain relevant today, underscoring the importance of ILCs in inflammation, tissue homeostasis, repair, and metabolism. More recent keywords include cancer, eosinophil, B cell, macrophage, double blind, heterogeneity, phenotype, and plasticity. These emerging keywords provide insights into disease mechanisms and the cell biology of ILCs. For instance, ILCs exhibit phenotypic and functional plasticity in response to environmental stimuli, which directs their heterogeneity in tissues. This plasticity is crucial for effective immune responses and may play significant roles in immune diseases, particularly cancer. For example, in the tumor microenvironment, natural killer cells can convert into ILC1s in response to transforming growth factor-beta, promoting tumor growth and metastasis. Keywords such as eosinophils, B cells, and macrophages highlight the importance of these immune cells in the immune response alongside ILCs, inducing different types of inflammation through cytokine secretion. These new keywords represent promising areas for future research, potentially revealing the applications of basic ILC biology studies, emphasizing the importance of transcriptional regulatory networks, and aiding in the development of new treatments for immune diseases.
In summary, research on ILCs has grown rapidly over the past decade and is poised to remain a hot topic in immunology. Key contributors to the field include Andrew N.J. McKenzie, David Artis, Marco Colonna, and Eric Vivier. The United States has been the leading contributor in terms of publications, facilitated by extensive academic exchange and research communication with other countries. Institut Pasteur ranks first among institutions worldwide in terms of publishing output on ILCs. Research related to ILCs in inflammation, tissue homeostasis, repair, and metabolism continues to be a focal point, while emerging topics such as cancer and transcriptional regulatory networks represent promising areas for future exploration.
doi.org/10.1097/CM9.0000000000000834
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