The literature data was obtained from the Web of Science Core Collection (WoSCC) database and PubMed database, and the search time was from 1 January 2000 to May 31, 2025. The search formula used was(TS = (psoriasis) AND TS = (“natural killer cell*” OR “NK cell*” OR “CD56+ lymphocyte*” OR “innate lymphoid cell*”).

Figure 2 presents the publication trends over the past 20 years. A total of 432 publications were identified in this period. No relevant studies were published between 2000 and 2002. The first sporadic publications appeared in 2003, and the number of publications gradually increased thereafter. From 2003 to 2010, the number of publications slowly rose from 3 to 12. The growth rate accelerated between 2011 and 2015, with the annual publication output increasing from 13 to 24. The period from 2016 to 2021 witnessed a sustained increase, with the annual publication count rising from 28 to a peak of 42, indicating a significant surge in research interest in “NK cells and psoriasis.” There was a slight decline in 2022 (32 publications) and a further decrease in 2023 to 25 publications. However, the number rebounded to 35 in 2024, suggesting that this research direction remains highly relevant. As of the search date in 2025, 12 related publications had already been released, and it is anticipated that the annual publication output will remain at a considerable level for the entire year. Overall, the field has demonstrated a consistent upward trend over the past two decades, particularly in the last decade, which has been a period of active research. To more accurately predict future trends, a polynomial fitting curve was plotted, as indicated by the red dashed line in Figure 2 . This curve suggests that publications in this field will continue to grow in the future. The coefficient of determination (R² = 0.7541) indicates that the model can explain 75.41% of the data variability, suggesting that this trend is highly informative. The increasing publication output highlights that NK cell immunotherapy in psoriasis is currently a focal point of research and holds promising prospects for future development.

Over the past 20 years, scholars from 60 countries/regions worldwide have contributed to publications related to NK cells and psoriasis. As shown in Figure 3 , the geographical distribution of publications is highly concentrated, primarily in developed countries in Europe, America, and East Asia. The United States has the highest number of publications (n = 112), followed by China (n = 57), Germany (n = 49), Japan (n = 43), Italy (n = 42), and the United Kingdom (n = 35). In terms of international collaboration, the United States holds a dominant position (cooperation intensity = 98), followed by Germany (n = 50) and the United Kingdom (n = 41), indicating that European and American countries have established stable collaborative research networks in this field.

Table 1 provides a detailed overview of the top 10 countries in terms of publication output, cooperation intensity, total citations, and average citations per publication. The United States not only has the highest total citations (n = 12,499) but also the highest average citations per publication (162.22), demonstrating its absolute advantage in producing high-impact research outcomes. Although China ranks second in publication output, its average citation count is 39.09, significantly lower than that of Germany (55.76), the United Kingdom (58.61), and Italy (51.73), indicating that there is room for improvement in research impact.

In summary, research on NK cells and psoriasis has formed a global pattern, with the United States and European countries as the academic core. While Asian countries have shown rapid growth in publication numbers, they still need to enhance international collaboration and accumulate high-quality research outcomes to strengthen their academic impact.

Over the past 20 years, a total of 2,558 authors from 806 institutions worldwide have published their research findings on NK cells in the field of psoriasis. Figure 4A presents the author collaboration network, in which Krueger, James G. (N = 8) is the most prolific author, while Sabat, Robert (C = 1,452) is the most cited author. During this period, five key teams centered around Krueger, James G., Bissonnette, Robert, Eyerich, Kilian, Brunner, Patrick M., and Christophe, Thierry have collectively propelled the development of this field, as shown in Figure 4B . Figure 4C illustrates the institutional collaboration network, with Rockefeller Univ (N = 10), Karolinska Inst (N = 9), Univ Calif San Francisco (N = 9), Univ Oxford (N = 9), and Trinity Coll Dublin (N = 8) being the most productive institutions in terms of publication output. The Univ Oxford (C = 1,983) is the most cited institution, and Univ Calif San Francisco and Univ Oxford have the highest cooperation intensity. The collective efforts of these authors and institutions have driven the rapid development of this field. The specific information of the authors and institutions with major contributions is shown in Table 2 .

A total of 217 journals have published research findings on NK cell immunotherapy in psoriasis. Figure 5A displays journals with citation counts greater than or equal to 3. Among them, Frontiers in Immunology (N = 32), International Journal of Molecular Sciences (N = 23), Journal of Investigative Dermatology (N = 16), Journal of Allergy and Clinical Immunology (N = 14), and British Journal of Dermatology (N = 12) are the most prolific journals in terms of publication output. The journals with the highest citation counts are Frontiers in Immunology (C = 2,151), Nature (C = 1,508), Journal of Allergy and Clinical Immunology (C = 1,419), European Journal of Immunology (C = 1,253), and International Journal of Molecular Sciences (C = 1,182). Figure 5B presents the co-citation network of journals, with J. Immunol (CC = 2,479), J. Invest. Dermatol. (CC = 1,620), J. Exp. Med. (CC = 1,359), Immunity (CC = 1,247), and Nat. Immunol. (CC = 1,112) being the most co-cited journals. The dual-map overlay of journals ( Figure 5C ) illustrates the citation relationships between citing and cited journals. The left side represents the clustering of citing journals, indicating the distribution of knowledge frontiers in the field, while the right side represents the clustering of cited journals, highlighting the important knowledge bases of the field. The orange path in Figure 5C indicates that journals from the fields of Molecular, Biology, and Genetics are most likely to be cited by journals related to Molecular, Biology, and Immunology, suggesting that the latest research involves substantial interdisciplinary studies. The green path indicates that journals from Molecular, Biology, and Genetics are most likely to be cited by journals related to Medicine, Medicinal, and Clinical, highlighting the multidisciplinary integration and convergence in this field.

Through the visualization analysis of keywords, we obtained key information in the current field. Figure 6A presents a bubble chart of keywords, with modules such as inflammation, atopic dermatitis, psoriatic arthritis, autoimmunity, skin, natural killer cells, innate lymphoid cells, IL - 17, innate immunity, and cytokines being the focal points of research. To further analyze the developmental trends of this field over time, Figure 6B shows a timeline of key clusters, indicating that 16 main clusters were formed in the field of NK cell immunotherapy and psoriasis research between 2018 and 2025.

Through keyword clustering analysis, we identified three key themes in the field of NK cell immunotherapy and psoriasis research. These themes not only cover the main threads of basic research and clinical translation but also reflect the research progress in immune regulation mechanisms and therapeutic target exploration.

Firstly, the autoimmune pathogenesis of psoriasis (core keywords: #4 autoimmune diseases, #9 immune response, #12 T cells, #14 psoriatic arthritis, #13 animal models) forms the theoretical foundation of the research. As a typical immune-mediated inflammatory disease, psoriasis is closely related to the dysfunction of the adaptive immune system, especially the abnormal activation of the Th17/IL-23 axis mediated by T cells. In-depth studies of T cell functions, IL - 17 production, and keratinocyte responses in animal models have provided an important basis for elucidating the regulatory role of NK cells in the immune network.

Secondly, the activation mechanisms of NK cells and innate immune signaling pathways (core keywords: #1 thymic stromal lymphopoietin, #3 activation, #10 major histocompatibility complex, #11 KIR, #0 Th17 cells) are important research directions in this field. Studies have shown that NK cells not only recognize target cells through KIR-MHC interactions but are also activated by cytokines such as TSLP and IL - 12, inducing Th17 responses and releasing IFN-γ, thereby amplifying and maintaining psoriatic inflammation. These studies provide theoretical support for revealing the cross-regulation mechanisms between innate and adaptive immunity.

Lastly, preclinical and clinical explorations of NK cell-targeted immunotherapy (core keywords: #2 clinical trial, #5 efficacy, #6 alpha, #7 monomethyl fumarate, #15 placebo-controlled trial, #8 arthritis) constitute the translational frontier of this research. In recent years, small molecule drugs (such as monomethyl fumarate) and biologics (such as IL - 17/IL-23 monoclonal antibodies) targeting NK cell functions have shown promising efficacy and safety in improving skin and joint lesions in psoriasis and psoriatic arthritis through multiple randomized controlled clinical trials, laying the foundation for the development of personalized immune intervention strategies.

In summary, the three key themes—from the basic research of psoriasis immune mechanisms to the inflammation amplification pathways mediated by NK cells and the clinical evaluation of immunotherapy—constitute the core knowledge framework of the field of “NK cell immunotherapy and psoriasis,” reflecting a systematic developmental trend from mechanism elucidation to clinical application.

By conducting an in-depth analysis of highly cited literature, we can further explore the developmental trends and key turning points of NK cell immune regulation in psoriasis research. Figure 7 presents a density map of articles cited more than 10 times, highlighting the important positions of some core articles in the co-citation network.

Buonocore et al. (2010) published a study in Nature (8) that first revealed that RORγt+, IL - 23R+ innate lymphoid cells (ILCs) can independently induce IL - 17 and IFN-γ expression in a T cell-deficient Rag– mouse model, driving the occurrence of intestinal inflammation in IL - 23-mediated inflammatory responses. This study clarified the pathogenic potential of ILCs in tissue-specific inflammation and provided a solid experimental basis for IL - 23 pathway-related autoimmune diseases such as psoriasis, occupying a core node in the co-citation network.

Gregory F. Sonnenberg et al. (2011) (9) systematically reviewed the functions of IL - 22 and its receptor pathway in immune regulation of barrier tissues, pointing out that IL - 22 plays a key role in maintaining immune homeostasis, antimicrobial defense, and tissue repair in the skin, gut, and respiratory tract. The study emphasized that the imbalance of IL - 22 expression is closely related to diseases such as psoriasis and inflammatory bowel disease, suggesting that the ILC family (including NK-like cells) participates in chronic inflammation and tissue homeostasis imbalance through the IL - 22 signaling axis. Their theoretical contributions are of great significance for NK cell function research and the development of targeted therapies.

Brunner et al. (2017) (10) reviewed the immune landscape of atopic dermatitis in the Journal of Allergy and Clinical Immunology, emphasizing the central role of ILC2 in TH2-dominated inflammatory responses. The article pointed out that AD is not only characterized by TH2 skewing but also involves TH17, TH22, and partial TH1 responses. ILC2 is significantly enriched in lesions, releasing cytokines such as IL - 5 and IL - 13, leading to barrier disruption and persistent inflammation. This review clearly supports the effectiveness of targeting the IL - 4/IL-13 pathway (e.g., dupilumab) and provides theoretical support for understanding the role of innate immune cells in chronic skin inflammation, including psoriasis.

Villani et al. (2018) (11) constructed a high-resolution atlas of human peripheral immune cells through single-cell RNA sequencing, identifying multiple functionally heterogeneous innate immune cell subsets, including different types of dendritic cells, monocytes, and NK cells. The study revealed the dynamic expression characteristics of ILC family cells in different inflammatory microenvironments, providing foundational resources for further exploring the functional differentiation and pathogenesis of NK cells in complex immune diseases such as psoriasis.

Teunissen et al. (2021) (12) used single-cell multi-omics strategies to analyze the immune features of memory T cells (TRM) and innate lymphoid cells (including ILCs and NK-like cells) in human skin tissue. The study found that psoriatic lesions contain a large number of CD49a+CD103+ NK-like cells that rapidly produce IL - 17 and IFN-γ in response to IL - 23, driving typical Th17-type inflammatory responses. This study proposed that “innate memory” cells may play a central role in psoriasis relapse mechanisms, offering new strategies for targeting TRM and ILCs to intervene in psoriasis relapse. The main findings of the top 20 highly cited articles are further summarized in Table 3 .