Increased circulating regulatory T cells and decreased follicular T helper cells are associated with colorectal carcinogenesis
ObjectiveColorectal cancer (CRC) is the third most prevalent cancer worldwide and is associated with high morbidity and mortality rates. Colorectal carcinogenesis occurs via the conventional adenoma-to-carcinoma and serrated pathways. Conventional T helper (Th) and innate lymphoid cells (ILCs) play...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1287632/full |
| _version_ | 1827374172455567360 |
|---|---|
| author | Qiao Meng Qiao Meng Yang Zhao Miao Xu Pingzhang Wang Jun Li Rongli Cui Weiwei Fu Weiwei Fu Shigang Ding Shigang Ding |
| author_facet | Qiao Meng Qiao Meng Yang Zhao Miao Xu Pingzhang Wang Jun Li Rongli Cui Weiwei Fu Weiwei Fu Shigang Ding Shigang Ding |
| author_sort | Qiao Meng |
| collection | DOAJ |
| description | ObjectiveColorectal cancer (CRC) is the third most prevalent cancer worldwide and is associated with high morbidity and mortality rates. Colorectal carcinogenesis occurs via the conventional adenoma-to-carcinoma and serrated pathways. Conventional T helper (Th) and innate lymphoid cells (ILCs) play vital roles in maintaining intestinal homeostasis. However, the contribution of these two major lymphoid cell populations and their associated cytokines to CRC development is unclear. Therefore, we aimed to analyze peripheral lymphocyte profiles during colorectal carcinogenesis.MethodsWe collected 86 blood samples concurrently, and pathologists confirmed the presence of various pathological conditions (i.e., HPs, adenoma, and carcinoma) using hematoxylin and eosin staining. Ten healthy donors were recruited as healthy controls (HCs) from the physical examination center. We performed flow cytometry on peripheral blood mononuclear cells collected from patients with various pathological conditions and the HCs, and cytokines (interleukin-2, interleukin-4, interleukin-5, interleukin-13, interleukin-17A, interleukin-17F, interleukin-22, interferon-γ, and tumor necrosis factor-α) were quantified. We also analyzed the published single-cell RNA sequence data derived from tissue samples from different stages of colorectal carcinogenesis.ResultsThe cytokine response in peripheral CD4+ T cells was upregulated during the carcinoma process. The frequency of peripheral regulatory T cells (Tregs) increased in the adenoma and carcinoma stages. While the T follicular helper (Tfh) cell proportion was downregulated in the adenoma and carcinoma processes. Thus, Th cell subsets, especially Tregs and Tfh cells, were involved in colonic diseases. Moreover, the immunological profile characteristics in the HPs were clarified.ConclusionWe comprehensively analyzed circulating ILCs and adaptive T-cell lymphocyte subtypes in colorectal carcinoma progression. Our results show the immunological profile characteristics and support the involvement of Th subsets, especially Treg and Tfh cell populations, in colonic diseases. These findings significantly enhance our understanding of the immune mechanisms underlying CRC and its precancerous lesions. Further investigation of the Treg and Tfh cells’ function in colorectal disease development will provide potential therapeutic targets for monitoring and preventing CRC development. |
| first_indexed | 2024-03-08T11:29:01Z |
| format | Article |
| id | doaj.art-64d3c0cb0e514bd2b5bf661a79e4e87e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T11:29:01Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-64d3c0cb0e514bd2b5bf661a79e4e87e2024-01-26T04:23:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011510.3389/fimmu.2024.12876321287632Increased circulating regulatory T cells and decreased follicular T helper cells are associated with colorectal carcinogenesisQiao Meng0Qiao Meng1Yang Zhao2Miao Xu3Pingzhang Wang4Jun Li5Rongli Cui6Weiwei Fu7Weiwei Fu8Shigang Ding9Shigang Ding10Department of Gastroenterology, Peking University Third Hospital, Beijing, ChinaBeijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases, Beijing, ChinaDepartment of Laboratory Medicine, Peking University Third Hospital, Beijing, ChinaBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, United StatesDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, NHC Key Laboratory of Medical Immunology (Peking University), Beijing, ChinaDepartment of Gastroenterology, Peking University Third Hospital, Beijing, ChinaDepartment of Gastroenterology, Peking University Third Hospital, Beijing, ChinaDepartment of Gastroenterology, Peking University Third Hospital, Beijing, ChinaBeijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases, Beijing, ChinaDepartment of Gastroenterology, Peking University Third Hospital, Beijing, ChinaBeijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases, Beijing, ChinaObjectiveColorectal cancer (CRC) is the third most prevalent cancer worldwide and is associated with high morbidity and mortality rates. Colorectal carcinogenesis occurs via the conventional adenoma-to-carcinoma and serrated pathways. Conventional T helper (Th) and innate lymphoid cells (ILCs) play vital roles in maintaining intestinal homeostasis. However, the contribution of these two major lymphoid cell populations and their associated cytokines to CRC development is unclear. Therefore, we aimed to analyze peripheral lymphocyte profiles during colorectal carcinogenesis.MethodsWe collected 86 blood samples concurrently, and pathologists confirmed the presence of various pathological conditions (i.e., HPs, adenoma, and carcinoma) using hematoxylin and eosin staining. Ten healthy donors were recruited as healthy controls (HCs) from the physical examination center. We performed flow cytometry on peripheral blood mononuclear cells collected from patients with various pathological conditions and the HCs, and cytokines (interleukin-2, interleukin-4, interleukin-5, interleukin-13, interleukin-17A, interleukin-17F, interleukin-22, interferon-γ, and tumor necrosis factor-α) were quantified. We also analyzed the published single-cell RNA sequence data derived from tissue samples from different stages of colorectal carcinogenesis.ResultsThe cytokine response in peripheral CD4+ T cells was upregulated during the carcinoma process. The frequency of peripheral regulatory T cells (Tregs) increased in the adenoma and carcinoma stages. While the T follicular helper (Tfh) cell proportion was downregulated in the adenoma and carcinoma processes. Thus, Th cell subsets, especially Tregs and Tfh cells, were involved in colonic diseases. Moreover, the immunological profile characteristics in the HPs were clarified.ConclusionWe comprehensively analyzed circulating ILCs and adaptive T-cell lymphocyte subtypes in colorectal carcinoma progression. Our results show the immunological profile characteristics and support the involvement of Th subsets, especially Treg and Tfh cell populations, in colonic diseases. These findings significantly enhance our understanding of the immune mechanisms underlying CRC and its precancerous lesions. Further investigation of the Treg and Tfh cells’ function in colorectal disease development will provide potential therapeutic targets for monitoring and preventing CRC development.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1287632/fullcolorectal canceradenomahyperplastic polypsT helper cellinnate lymphoid cells |
| spellingShingle | Qiao Meng Qiao Meng Yang Zhao Miao Xu Pingzhang Wang Jun Li Rongli Cui Weiwei Fu Weiwei Fu Shigang Ding Shigang Ding Increased circulating regulatory T cells and decreased follicular T helper cells are associated with colorectal carcinogenesis Frontiers in Immunology colorectal cancer adenoma hyperplastic polyps T helper cell innate lymphoid cells |
| title | Increased circulating regulatory T cells and decreased follicular T helper cells are associated with colorectal carcinogenesis |
| title_full | Increased circulating regulatory T cells and decreased follicular T helper cells are associated with colorectal carcinogenesis |
| title_fullStr | Increased circulating regulatory T cells and decreased follicular T helper cells are associated with colorectal carcinogenesis |
| title_full_unstemmed | Increased circulating regulatory T cells and decreased follicular T helper cells are associated with colorectal carcinogenesis |
| title_short | Increased circulating regulatory T cells and decreased follicular T helper cells are associated with colorectal carcinogenesis |
| title_sort | increased circulating regulatory t cells and decreased follicular t helper cells are associated with colorectal carcinogenesis |
| topic | colorectal cancer adenoma hyperplastic polyps T helper cell innate lymphoid cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1287632/full |
| work_keys_str_mv | AT qiaomeng increasedcirculatingregulatorytcellsanddecreasedfollicularthelpercellsareassociatedwithcolorectalcarcinogenesis AT qiaomeng increasedcirculatingregulatorytcellsanddecreasedfollicularthelpercellsareassociatedwithcolorectalcarcinogenesis AT yangzhao increasedcirculatingregulatorytcellsanddecreasedfollicularthelpercellsareassociatedwithcolorectalcarcinogenesis AT miaoxu increasedcirculatingregulatorytcellsanddecreasedfollicularthelpercellsareassociatedwithcolorectalcarcinogenesis AT pingzhangwang increasedcirculatingregulatorytcellsanddecreasedfollicularthelpercellsareassociatedwithcolorectalcarcinogenesis AT junli increasedcirculatingregulatorytcellsanddecreasedfollicularthelpercellsareassociatedwithcolorectalcarcinogenesis AT ronglicui increasedcirculatingregulatorytcellsanddecreasedfollicularthelpercellsareassociatedwithcolorectalcarcinogenesis AT weiweifu increasedcirculatingregulatorytcellsanddecreasedfollicularthelpercellsareassociatedwithcolorectalcarcinogenesis AT weiweifu increasedcirculatingregulatorytcellsanddecreasedfollicularthelpercellsareassociatedwithcolorectalcarcinogenesis AT shigangding increasedcirculatingregulatorytcellsanddecreasedfollicularthelpercellsareassociatedwithcolorectalcarcinogenesis AT shigangding increasedcirculatingregulatorytcellsanddecreasedfollicularthelpercellsareassociatedwithcolorectalcarcinogenesis |