Medina-Castro Lab
The intestinal immune system in cancer and immune regulation
Standing at the intersection of Nutrition, Proteomics, and Immunology, our lab studies mucosal regulation in cancer, inflammation, and immunity. Intestinal immune homeostasis is maintained by a fine balance between the pro- and anti-inflammatory responses to microbiota. An extensive network of antigen presenting cells and effector cells tightly regulate these responses. We focus primarily on 1) the role of nutrition on immune responses and 2) macrophages regulation of intestinal T cells and epithelial cells, in health and disease.
Our group employs clinical interventions, immuno-proteomic, flow cytometry, proteomics and genomic methods, cell biology, biochemistry and in vivo models to reveal new intestinal immune regulation mechanisms.
We combine our expertise to gain novel insight on basic research questions, and we aim for translating our findings into clinical applications and therapeutic interventions to promote human health.
Our most recent papers are:
Gutiérrez Salmeán G, Delgadillo González M, Rueda Escalona AA, Leyva Islas JA, Castro-Eguiluz D.
Front Oncol 14:1383258
doi 10.3389/fonc.2024.1383258, PubMed
Gut microbiota plays a crucial role in modulating immune responses, including effector response to infection and surveillance of tumors. This article summarizes the current scientific evidence on the effects of supplementation with prebiotics, probiotics, and synbiotics on high-risk human papillomavirus (HPV) infections, precancerous lesions, and various stages of cervical cancer development and treatment while also examining the underlying molecular pathways involved. Our findings indicate that a higher dietary fiber intake is associated with a reduced risk of HPV infection, while certain probiotics have shown promising results in clearing HPV-related lesions. Additionally, certain strains of probiotics, prebiotics such as inulin and fructo-oligosaccharides, and synbiotics decrease the frequency of gastrointestinal adverse effects in cervical cancer patients. These agents attain their results by modulating crucial metabolic pathways, including the reduction of inflammation and oxidative stress, promoting apoptosis, inhibiting cell proliferation, and suppressing the activity of oncogenes, thus attenuating tumorigenesis. We conclude that although further human studies are necessary, robust evidence in preclinical models demonstrates that prebiotics, probiotics, and synbiotics play an essential role in cervical cancer, from infection to carcinogenesis and its medical treatment. Consequently, we strongly recommend conducting high-quality clinical trials using these agents as adjuvants since they have proven safe.
Manzanares-Meza LD, Gutiérrez-Román CI, Jiménez-Pineda A, Castro-Martínez F, Patiño-López G, Rodríguez-Arellano E, Valle-Rios R, Ortíz-Navarrete VF, Medina-Contreras O
Front Immunol 13, 979749
doi 10.3389/fimmu.2022.979749, PubMed
Mucosal innate immunity functions as the first line of defense against invading pathogens. Members of the IL-1 family are key cytokines upregulated in the inflamed mucosa. Inflammatory cytokines are regulated by limiting their function and availability through their activation and secretion mechanisms. IL-1 cytokines secretion is affected by the lack of a signal peptide on their sequence, which prevents them from accessing the conventional protein secretion pathway; thus, they use unconventional protein secretion pathways. Here we show in mouse macrophages that LPS/ATP stimulation induces cytokine relocalization to the plasma membrane, and conventional secretion blockade using monensin or Brefeldin A triggers no IL-36\(\gamma\) accumulation within the cell. In silico modeling indicates IL-36\(\gamma\) can pass through both the P2X7R and Gasdermin D pores, and both IL-36\(\gamma\), P2X7R and Gasdermin D mRNA are upregulated in inflammation; further, experimental blockade of these receptors limits IL-36\(\gamma\) release. Our results demonstrate that IL-36\(\gamma\) is secreted mainly by an unconventional pathway through membrane pores formed by P2X7R and Gasdermin D.
Denisse Castro-Eguiluz is a researcher for México at the National Cancer Institute, where she works on cervical cancer. Oscar Medina-Contreras is a medical sciences researcher at Mexico Children’s Hospital, where he works on mucosal immunology.