CXCL10+ peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter

Prizant, Hen; Patil, Nilesh; Negatu, Seble G; Bala, Noor; McGurk, Alexander I.; Leddon, Scott A; Hughson, Angela; McRae, Tristan D; Gao, Yurong; Livingstone, Alexandra; Groom, Joanna R; Luster, Andrew D.; Fowell, Deborah J.

doi:10.1016/j.celrep.2021.109523

Cited by 20 publications

(36 citation statements)

References 53 publications

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“…It is unclear at present if these sites originate from an existing pre‐positioned steady‐state niche, akin to the advential cuff. At least in the skin, 4 they are seen “scattered” across large areas of the inflamed tissue suggesting they may serve to cast a wide net for initial effector T cell recruitment. Alternatively, the distribution of the activation niches could be stochasitic and directed by the incoming T cells themselves.…”

Section: Discussionmentioning

confidence: 99%

“…Niche visibility appears to be enhanced by a T cell–mediated positive feedback loop, where cytokines secreted by T cells in the niche upregulate local chemokine expression 4 . At early stages in the immune response to infection, antigen‐specific effector T cells entering the infected tissue are at low frequency.…”

Section: The Niche Advantagementioning

confidence: 99%

“…A growing body of evidence points to the de novo assembly of microanatomical activation hubs located perivascularly that are induced following immune challenge and that underpin T cell immunity within inflamed tissues. 4,5,7,8,86,[117][118][119]…”

Section: Induced Activation Nichesmentioning

confidence: 99%

“…The induction of innate signals, such as type 1 interferons, initiate the activation and recruitment of myeloid subsets to the perivascular space, where local niche-specific chemokine production and antigen presentation optimizes encounter with incoming effector T cells. 4,5 It is not yet known if the induced perivascular niche arises from any strategic positioning that might optimize enrichment of antigen, as seen in the SCS of the LN or the adventitial cuff. In the skin, following complete Freund's adjuvant (CFA)-protein immunization, perivascular activation niches "popped up" throughout the ear pinna, often thousands of microns away from the antigen depot, suggesting they may be broadly induced to maximize opportunities for antigen encounter.…”

Section: Perivascular Activation Nichesmentioning

confidence: 99%

“…120,121 In a recent study, the use of a CXCL9/CXCL10 dual reporter mouse (REX3) 32 and intravital multiphoton microscopy enabled dissection of the cellular dynamics within the perivascular niche of the inflamed dermis. 4 Single-cell analysis of colorectal cancers in humans 8 also identified a CXCL10 + perivascular niche associated with an accumulation of IFNγ + effector T cells (see discussion below).…”

Section: Cxcr3 Expression By Effector T Cells Was Implicated In Posit...mentioning

confidence: 99%

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T cell activation niches—Optimizing T cell effector function in inflamed and infected tissues*

Bala

McGurk

Zilch

et al. 2021

Immunological Reviews

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Successful immunity to infection, malignancy, and tissue damage requires the coordinated recruitment of numerous immune cell subsets to target tissues. Once within the target tissue, effector T cells rely on local chemotactic cues and structural cues from the tissue matrix to navigate the tissue, interact with antigen‐presenting cells, and release effector cytokines. This highly dynamic process has been “caught on camera” in situ by intravital multiphoton imaging. Initial studies revealed a surprising randomness to the pattern of T cell migration through inflamed tissues, behavior thought to facilitate chance encounters with rare antigen‐bearing cells. Subsequent tissue‐wide visualization has uncovered a high degree of spatial preference when it comes to T cell activation. Here, we discuss the basic tenants of a successful effector T cell activation niche, taking cues from the dynamics of Tfh positioning in the lymph node germinal center. In peripheral tissues, steady‐state microanatomical organization may direct the location of “pop‐up” de novo activation niches, often observed as perivascular clusters, that support early effector T cell activation. These perivascular activation niches appear to be regulated by site‐specific chemokines that coordinate the recruitment of dendritic cells and other innate cells for local T cell activation, survival, and optimized effector function.

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Section: Discussionmentioning

confidence: 99%

Section: The Niche Advantagementioning

confidence: 99%