A Subset of CCL25-Induced Gut-Homing T Cells Affects Intestinal Immunity to Infection and Cancer

Abstract

Protective immunity relies upon differentiation of T cells into the appropriate subtype required to clear infections and efficient effector T cell localization to antigen-rich tissue. Recent studies have highlighted the role played by subpopulations of tissue-resident memory (T RM ) T lymphocytes in the protection from invading pathogens. The intestinal mucosa and associated lymphoid tissue are densely populated by a variety of resident lymphocyte populations, including αβ and γδ CD8 + intraepithelial T lymphocytes (IELs) and CD4 + T cells. While the development of intestinal γδ CD8 + IELs has been extensively investigated, the origin and function of intestinal CD4 + T cells have not been clarified. We report that CCR9 signals delivered during naïve T cell priming promote the differentiation of a population of IFN-γ-producing memory CD4 + T cells, which displays a T RM molecular signature, preferentially localizes to the gastrointestinal (GI) tract and associated lymphoid tissue and cannot be mobilized by remote antigenic challenge. We further show that this population shapes the immune microenvironment of GI tissue, thus affecting effector immunity in infection and cancer.

CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of Receptors CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 Ligands

“…This chemokine is important for the correct function of the thymus [ 279 , 280 ]. Due to the expression of CCL25 in the gastrointestinal tract, lymphocyte homing to the tissues of this system is one of the main functions of the CCL25→CCR9 axis [ 281 , 282 , 283 ]. This is of great importance in the immunological functions of the intestinal and gastric mucosa.…”

The Roles of CCR9/CCL25 in Inflammation and Inflammation-Associated Diseases

“…CD4 + CCR9 + T helper cells express high amounts of interleukin 21 and induce T cell costimulatory factor, transcription factor B cell CLL/lymphoma 6 (Bcl-6), and Maf, which are local features of autoimmune diseases that affect the accessory organs of the digestive system ( McGuire et al, 2011 ). The CCR9 signal transmitted during the startup of naïve T cells promotes the differentiation of memory CD4 + T cells that produce α 4 β + 7 IFN-γ, increasing the immune microenvironment in gastrointestinal tissues, thereby affecting effector immunity in infections and cancer ( Fu et al, 2019 ). Notably, Chen et al (2020) used tumor acidity-responsive nanoparticle delivery system (NP-siCD47/CCL25) to discharge CCL25 protein and CD47 siRNA in tumors to enhance CD47 targeted immunotherapy.…”

Identification of Novel Tumor-Microenvironment-Regulating Factor That Facilitates Tumor Immune Infiltration in Colon Cancer

“…Thus, the 802 DEGs were subjected to GO and KEGG pathway analysis. Most genes, such as CCL25, CLEC2A, NLRP4, CTNNA2, CALCA, and KCNE1B were reported participating in tumor microenvironment modulating 15 , 16 , 17 , 18 . Consistently, GO term also revealed that these genes were interacted with immune cells in remodeling immune microenvironment of colon cancer: Antimicrobial humoral response (GO: 0019730), humoral immune response (GO: 0006959), cell killing (GO: 0001906).…”