A Multimodal Generative AI Copilot for Human Pathology.

The field of computational pathology[1,2] has witnessed remarkable progress in the development of both task-specific predictive models and task-agnostic self-supervised vision encoders[3,4]. However, despite the explosive growth of generative artificial intelligence (AI), there has been limited study on building general purpose, multimodal AI assistants and copilots[5] tailored to pathology. Here we present PathChat, a vision-language generalist AI assistant for human pathology. We build PathChat by adapting a foundational vision encoder for pathology, combining it with a pretrained large language model and finetuning the whole system on over 456,000 diverse visual language instructions consisting of 999,202 question-answer turns. We compare PathChat against several multimodal vision language AI assistants and GPT4V, which powers the commercially available multimodal general purpose AI assistant ChatGPT-4[7]. PathChat achieved state-of-the-art performance on multiple-choice diagnostic questions from cases of diverse tissue origins and disease models. Furthermore, using open-ended questions and human expert evaluation, we found that overall PathChat produced more accurate and pathologist-preferable responses to diverse queries related to pathology. As an interactive and general vision-language AI Copilot that can flexibly handle both visual and natural language inputs, PathChat can potentially find impactful applications in pathology education, research, and human-in-the-loop clinical decision making.

Enteric Glia Regulate Lymphocyte Activation via Autophagy-Mediated MHC-II Expression.

BACKGROUND & AIMS: Enteric glial cells express type II major histocompatibility complex (MHC-II) molecules in Crohn's disease and Chagas disease, but it is unclear whether the expressed molecules are functional. We examined the capabilities of enteric glia to act as an antigen-presenting cell in vivo and whether glial MHC-II has immunomodulatory effects. METHODS: We generated Sox10CreERT2;IABfl/fl mice to ablate MHC-II in enteric glia after exposure to tamoxifen. We measured phagocytic activity and autophagy activation to assess potential peptide sources loaded onto glial MHC-II and measured T- and B-lymphocyte activation and serum and colonic tissue cytokine levels to study enteric glial immunomodulatory capabilities. RESULTS: Enteric glia express MHC-II molecules in response to a subclinical dose of interferon-γ and lipopolysaccharide in vivo. Glial MHC-II expression contributes to effective B-lymphocyte and T-lymphocyte activation with marked effects on T-helper cell (Th)17 and regulatory T cell subtypes. No effect on Th1 or Th2 subtypes was observed. Enteric glial MHC-II does not have a major effect on serum or colonic tissue cytokine levels but may influence local cytokine levels. Glial MHC-II expression requires the activation of autophagy pathways, but activating autophagy alone is not sufficient to drive glial MHC-II expression. CONCLUSIONS: Enteric glia express MHC-II as a mechanism to tune intestinal immune responses. Glial autophagy is triggered in response to proinflammatory stimuli and induces glial antigen presentation, which functions to modulate the activation of T-lymphocyte subsets involved in tolerance. These observations suggest that enteric glia may express MHC-II to maintain immune homeostasis during inflammatory conditions such as Crohn's disease.

Potential roles of enteric glia in bridging neuroimmune communication in the gut.

The enteric nervous system (ENS) is a network of neurons and glia that controls ongoing gastrointestinal (GI) functions. Damage or injury to the ENS can lead to functional GI disorders. Current data support the conclusion that many functional GI disorders are caused by an imbalance between gut microbes and the immune system, but how the ENS is involved in these interactions is less understood. Because of the proximity of the ENS to bacteria and other foreign antigens in the GI tract, it is important to prevent the passage of these antigens through the GI epithelium. If any foreign compounds manage to pass through the GI epithelium, an immune response is triggered to prevent injury to the ENS and underlying structures. However, careful modulation of the inflammatory response is required to allow for adequate elimination of foreign antigens while avoiding inappropriate overactivation of the immune system as in autoimmune disorders. Enteric neurons and glial cells are capable of performing these immunomodulatory functions to provide adequate protection to the ENS. We review recent studies examining the interactions between the ENS and the immune system, with specific focus on enteric glial cells and their ability to modulate inflammation in the ENS.