Tissue immunity broadcasts near and far

Research advances in tissue immunology have begun to decipher how organ physiology is integrated with resident immune cells during tissue development, healthspan and disease states. Here, we review a selection of studies from 2019 that highlight how resident lymphocytes communicate with epithelia, neurons and stromal cells in tissues to coordinate regional and systemic remodelling in response to local perturbations.

Key advances

  • Skin epidermal innate lymphoid cells (ILCs) represent a transitional subset with features of both ILC2s and ILC3s that limit sebaceous gland growth and regulate the skin microbiome.

  • Sensory neurons are a rapid means of broadcasting local tissue perturbations to regional sites, acting through innate lymphocytes to prime these sites for subsequent challenge.

  • Mesenteric lymph nodes drain discrete regions of the intestine, maintaining an anatomical patterning that promotes immune tolerance at proximal sites and immune effector function at distal sites.

  • Mesenchymal stromal cells communicate with tissue-resident lymphocytes within distinct niches in adipose tissue, lung and elsewhere, contributing to organ function and regional immunity.

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Fig. 1: Broadcasting tissue immunity.


  1. 1.

    Fan, X. & Rudensky, A. Y. Hallmarks of tissue-resident lymphocytes. Cell 164, 1198–1211 (2016).

  2. 2.

    Kobayashi, T. et al. Homeostatic control of sebaceous glands by innate lymphoid cells regulates commensal bacteria equilibrium. Cell 176, 982–997.e16 (2019).

  3. 3.

    Schneider, C. et al. Tissue-resident group 2 innate lymphoid cells differentiate by layered ontogeny and in situ perinatal priming. Immunity 50, 1425–1438.e5 (2019).

  4. 4.

    Cohen, J. A. et al. Cutaneous TRPV1+ neurons trigger protective innate type 17 anticipatory immunity. Cell 178, 919–932.e14 (2019).

  5. 5.

    Kashem, S. W. et al. Nociceptive sensory fibers drive interleukin-23 production from CD301b+ dermal dendritic cells and drive protective cutaneous immunity. Immunity 43, 515–526 (2015).

  6. 6.

    Esterházy, D. et al. Compartmentalized gut lymph node drainage dictates adaptive immune responses. Nature 569, 126–130 (2019).

  7. 7.

    Dahlgren, M. W. et al. Adventitial stromal cells define group 2 innate lymphoid cell tissue niches. Immunity 50, 707–722.e6 (2019).

  8. 8.

    Rana, B. M. J. et al. A stromal cell niche sustains ILC2-mediated type-2 conditioning in adipose tissue. J. Exp. Med. 216, 1999–2009 (2019).

  9. 9.

    Mahlakõiv, T. et al. Stromal cells maintain immune cell homeostasis in adipose tissue via production of interleukin-33. Sci. Immunol. 4, eaax0416 (2019).

  10. 10.

    Spallanzani, R. G. et al. Distinct immunocyte-promoting and adipocyte-generating stromal components coordinate adipose tissue immune and metabolic tenors. Sci. Immunol. 4, eaaw3658 (2019).

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The authors acknowledge discussion with members of the Molofsky and Locksley laboratories and support from the National Institutes of Health (to A.B.M. and R.M.L.), Howard Hughes Medical Institute (to R.M.L.) and the Sandler Asthma Basic Research Center (to A.B.M. and R.M.L.).

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Correspondence to Ari B. Molofsky or Richard M. Locksley.

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The authors declare no competing interests.

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Molofsky, A.B., Locksley, R.M. Tissue immunity broadcasts near and far. Nat Rev Immunol 20, 93–94 (2020). https://doi.org/10.1038/s41577-019-0250-4

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