Stem cells repurpose proliferation to contain a breach in their niche barrier.

Adult stem cells are responsible for life-long tissue maintenance. They reside in and interact with specialized tissue microenvironments (niches). Using murine hair follicle as a model, we show that when junctional perturbations in the niche disrupt barrier function, adjacent stem cells dramatically change their transcriptome independent of bacterial invasion and become capable of directly signaling to and recruiting immune cells. Additionally, these stem cells elevate cell cycle transcripts which reduce their quiescence threshold, enabling them to selectively proliferate within this microenvironment of immune distress cues. However, rather than mobilizing to fuel new tissue regeneration, these ectopically proliferative stem cells remain within their niche to contain the breach. Together, our findings expose a potential communication relay system that operates from the niche to the stem cells to the immune system and back. The repurposing of proliferation by these stem cells patch the breached barrier, stoke the immune response and restore niche integrity.

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The Microbiome in Atopic Dermatitis

As an interface with the environment, the skin is a complex ecosystem, colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens such as S. aureus and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized, as microorganisms can modulate innate, as well as adaptive, immune responses. Host-commensal interactions also have an impact on the developing immune system in infants and subsequently the occurrence of diseases such as asthma and atopic dermatitis. Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with atopic dermatitis, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria such as S. aureus. Early clinical studies suggest that topical application of commensal organisms (e.g., S. hominis or R. mucosa) reduces atopic dermatitis severity and support an important role for commensals in decreasing S. aureus colonization in patients with atopic dermatitis. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders such as atopic dermatitis may result in novel therapeutic strategies.

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Commensal-dendritic cell interactions specifies a unique protective skin immune signature.

Naik S*, Bouladoux N*, Linehan J, Han SJ, Harrison OJ, Wilhelm C, Conlan S, Himmelfarb S, Byrd A, Deming C, Quinones M, Brenchley JM, Kong H, Tussiwand R, Murphy KM, Merad M, Segre JA and Belkaid Y. Commensal-dendritic cell interactions specifies a unique protective skin immune signature. Nature. 520(7545): 104-108 April 2015.

Here we show that defined commensals dominantly affect skin immunity and identify the cellular mediators involved in this specification.This interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific immunity and pathologies.

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Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment.

Iida N, Dzutsev A, Stewart A, Bouladoux N, Smith L, Salcedo R, Cardone M, Back T, Kiu H, Cramer S, Naik S, Patri A, Wang E, Marincola FM, Belkaid Y, Trinchieri G and Goldszmid RS. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 342(6161):967-70. Nov, 2013

The gut microbiota influences both local and systemic inflammation. Inflammation contributes to development, progression, and treatment of cancer, but it remains unclear whether commensal bacteria affect inflammation in the sterile tumor microenvironment. Here, we show that disruption of the microbiota impairs the response of subcutaneous tumors to CpG-oligonucleotide immunotherapy and platinum chemotherapy.

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Intraluminal containment of commensal outgrowth in the gut during infection induced dysbiosis.

Molloy MJ*, Grainger JR*, Bouladoux N*, Hand TW, Naik S, Quimones M, Dzutsev AK, Gao JL, Trinchieri G, Murphy PM and Belkaid Y. Intraluminal containment of commensal outgrowth in the gut during infection induced dysbiosis. Cell Host Microbe. 14(3):318-28. Sept, 2013

Shifts in commensal microbiota composition are emerging as a hallmark of gastrointestinal inflammation. In particular, outgrowth of γ-proteobacteria has been linked to the etiology of inflammatory bowel disease and the pathologic consequences of infections. Here we show that following acute Toxoplasma gondiigastrointestinal infection of mice, control of commensal outgrowth is a highly coordinated process involving both the host response and microbial signals.

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