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immunology

tissue immunity

The tissue immunity team at the Allen Institute uncovers how immune cells adapt to tissues to provide protection, revealing fundamental principles that guide the development of new strategies to enhance or restrain immunity at specific sites.
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goals and approach

Our goal is to build a comprehensive spatial map of tissue immunity and to translate mechanistic insights into new strategies to guide immune responses. These approaches aim to direct immune cells to target tissues, enhance protective immunity at sites of infection or tumors, or selectively dampen harmful inflammation in autoimmune and inflammatory diseases.

The Tissue Immunity team at the Allen Institute investigates how immune cells establish and maintain protection within tissues. While traditional immunology has focused on the blood and lymphoid organs, critical immune responses occur directly at tissue sites such as the intestine, lung, and skin. Our research centers on tissue-resident memory T cells (TRM cells), a specialized population that remains embedded within tissues to provide rapid and durable local immunity.

We integrate studies in human tissues and genetic mouse models, combining the strengths of both systems to uncover the principles that govern tissue-specific immune adaptation. Fundamental mechanistic studies in mice allow precise dissection of the molecular and cellular pathways that drive immune cell residency, while human research captures the complexity and diversity of tissue immunity in health and disease. Using spatial transcriptomics, single-cell profiling, genetic perturbations, and computational analysis, we define how tissue environments imprint immune cell fate, function, and organization.

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projects/

Spatial Regulation of Tissue-Resident Memory T Cells

Our team investigates how the location of immune cells within tissues governs their function, using advanced spatial transcriptomics and genetic perturbation strategies. Our recent work, published in Nature, revealed that tissue-resident memory CD8 T cells adopt distinct functions depending on their position within the intestinal architecture, highlighting how tissue niches imprint immune cell fate and behavior​​. Regional signaling, cytokine gradients, and cell–cell interactions shape whether T cells differentiate into effector-like or memory-like subsets, highlighting how tissue niches imprint immune cell fate and function. Building on these findings, we are now exploring strategies in mouse models to target these pathways. By analyzing transcription factors and molecular circuits that regulate spatial differentiation and positioning, we aim to identify approaches to enhance protective immunity or modulate pathological immune responses at specific tissue sites.

Human Tissue Immune Map

The developing mouse brain is a foundational experimental model for investigation of the origins of cell types in the mammalian brain. We are generating a comprehensive, spatially and temporally resolved, cellular-resolution atlas of the whole developing mouse brain, spanning the entire period of embryonic and postnatal brain development, using single-cell and spatial transcriptomic and multiomic technologies. This work will enable a deep understanding of the mechanisms of mammalian brain development and neurodevelopmental disorders. This project is supported by the BRAIN Initiative Cell Atlas Network (BICAN) with funding from NIH/NIMH.

tissue immunity publications

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tissue immunity team

Nathan Kieswetter
Scientist I
Kennidy Takehara
Scientist I
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