{"doi":"10.1111/imr.13363","title":"Autoimmunity and the microbiome","abstract":"The gut microbiome is a diverse collection of bacteria, fungi, and viruses that have coevolved with the immune system. The microbiome plays a central role in shaping immunologic development as well as regulating other physiologic processes, including metabolic and neurologic functions. Several of the key mechanisms relate to (a) the activation of innate immune system and induction of specific immune cell subsets by pathogen-associated molecular patterns (PAMPS); (b) microbial adherence to the intestinal epithelia surface; (c) the secretion of immunomodulatory metabolites; and (d) biomimicry. While these interactions may be crucial for normal immunologic development, overactivation of these same microbe-immune signaling pathways may lead to the induction of tissue inflammation and autoimmunity.1 This special issue will cover the mechanisms by which the gut microbiome influences autoimmune diseases, including type 1 diabetes (T1D),2, 3 systemic lupus erythematosus (SLE),4, 5 rheumatoid arthritis (RA),6, 7 and multiple sclerosis (MS).8-10 Also covered are considerations for host factors such as genetics, aging, and sex, as well as translation for prevention and treatment of autoimmune disease (Figure 1). Th17 cells are highly responsive to the gut microbiota,11 play a central role in autoimmunity, and also play important roles in tissue repair, and protection against infection.1 Major questions in the field relate to (a) what factors determine a pathogenic versus homeostatic/protective Th17 cells and (b) what role the gut microbiota play in shaping these responses. This topic is reviewed by Schnell in this special issue.1 In groundbreaking work using single cell sequencing, Schnell and colleagues identified a novel stem-like and self-renewing Th17 population denoted by TCF1+ transcription factor and SLAMF6+ receptor expression.12 The stem-like SLAMF6+ Th17 cells largely reside in the intestinal mucosa, and migrate to the intestinal mucosal following adoptive transfer. Further, they are depleted by oral antibiotics, suggesting that the gut microbiota plays an essential role in maintaining them. In models of autoimmune diseases, stem-like Th17 cells can differentiate into pathogenic CXCR6+ Th17 cells that traffic to the extraintestinal sites where they induce tissue inflammation (e.g., the CNS in EAE). Other studies confirm the finding of the presence of stem-like SLAMF6+ Th17 cells in the gut and demonstrate that they can also differentiate into IL-10 producing Th17 cells, which have anti-inflammatory functions. This first article in our special issue on the Autoimmunity and the Microbiome sets the stage to understand specific signaling mechanisms at the mucosal interface that may have broad implications in tissue homeostasis and tissue inflammation. Type 1 diabetes is mediated by autoreactive effector T cells that induce destruction of β cells in the pancreas, diminishing insulin production.2, 3 In this issue, Yau and Danska discuss immunologic mechanisms by which the early-life microbiota modifies disease risk. Fuhri, Nieuwdorp and colleagues discuss the potential of fecal microbiota transplants for treating T1D.3 While several genetic variations have been linked with T1D risk, including specific HLA haplotypes, the disease penetrance is variable.2 Studies from the Danska laboratory have shown that sex-specific microbiota interactions can shape T1D incidence in animal models.13 Furthermore, there are distinct geographic variations in disease prevalence, including lower rates in China, Venezuela, and Russia and higher rates in Sardinia and Finland. Because the microbiota can vary by region, researchers have hypothesized that this may be explained in part by the differences in gut microbiome. Emerging data suggest that the first 6 months of life in humans and the first 4 weeks in mice during the nursing period represents a critical window of both immunologic2 and metabolic14 programming, in which early life microbes can shape long","journal":"Immunological Reviews","year":2024,"id":468510,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":25068,"name":"Vijay Kuchroo","orcid":"0000-0002-5993-0427","position":1,"is_corresponding":false},{"id":745777,"name":"Laura M. Cox","orcid":"0000-0002-9564-9894","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":null,"created_at":"2026-07-19T02:05:23.500722Z","pmid":"38980198","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}