Our skin is the interface through which we mediate lifelong interactions with our surrounding environment. Initial development of the skin's epidermis, adnexal structures, and barrier function is necessary for normal cutaneous microbial colonization, immune development, and prevention of disease. Early life microbial exposures can have unique and long-lasting impacts on skin health. The identity of neonatal skin microbes and the context in which they are first encountered, i.e., through a compromised skin barrier or in conjunction with cutaneous inflammation, can have additional short- and long-term health consequences. Here, we discuss key attributes of infant skin and endogenous and exogenous factors that shape its relationship to the early life cutaneous microbiome, with a focus on their clinical implications.

Early-life establishment of tolerance to commensal bacteria at barrier surfaces carries enduring implications for immune health but remains poorly understood. Here, we showed that tolerance in skin was controlled by microbial interaction with a specialized subset of antigen-presenting cells. More particularly, CD301b+ type 2 conventional dendritic cells (DCs) in neonatal skin were specifically capable of uptake and presentation of commensal antigens for the generation of regulatory T (Treg) cells. CD301b+ DC2 were enriched for phagocytosis and maturation programs, while also expressing tolerogenic markers. In both human and murine skin, these signatures were reinforced by microbial uptake. In contrast to their adult counterparts or other early-life DC subsets, neonatal CD301b+ DC2 highly expressed the retinoic-acid-producing enzyme, RALDH2, the deletion of which limited commensal-specific Treg cell generation. Thus, synergistic interactions between bacteria and a specialized DC subset critically support early-life tolerance at the cutaneous interface.

Purpose

To examine whether interpersonal aspects of patient-clinician interactions, such as patient-perceived medical discrimination, clinician mistrust, and treatment decision-making contribute to racial/ethnic/educational disparities in breast cancer care.

Methods

A telephone interview was administered to 542 Asian/Pacific Islander (API), Black, Hispanic, and White women identified through the Greater Bay Area Cancer Registry, ages 20 and older diagnosed with a first primary invasive breast cancer. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated from logistic regression models that assessed associations between race/ethnicity/education, medical discrimination, clinician mistrust, and treatment decision-making with concordance to breast cancer treatment guidelines (guideline-concordant treatment) and perceived quality of care (pQoC).

Results

Approximately three-quarters of women received treatment that was guideline-concordant (76.6%) and reported that their breast cancer care was excellent (72.1%). Non-college-educated Black women had lower odds of guideline-concordant care (aOR (CI) = 0.29 (0.12-0.67)) vs. college-educated White women. Odds of excellent pQoC were lower among the following: college-educated Hispanic women (aOR (CI) = 0.09 (0.02-0.47)) and API women regardless of education (aORs ≤ 0.50) vs. college-educated White women, women reporting low and moderate levels of discrimination (aORs ≤ 0.44) vs. none, and women reporting any clinician mistrust (aOR (CI) = 0.50 (0.29-0.88)) vs. none. Disparities in guideline-concordant care and pQoC persisted after controlling for medical discrimination, clinician mistrust, and decision-making.

Conclusions

Interpersonal aspects of the patient-clinician interaction had an impact on pQoC but not receipt of guideline-concordant treatment and did not explain disparities in either outcome.

Implications for cancer survivors

Although breast cancer survivors' interpersonal interactions with clinicians did not influence receipt of appropriate treatment, intervention strategies to improve patient-clinician relations may help attenuate disparities in survivors' pQoC.

Resident microbes in skin and gut predominantly impact local immune cell function during homeostasis. However, colitis-associated neutrophilic skin disorders suggest possible breakdown of this compartmentalization with disease. Using a model wherein neonatal skin colonization by Staphylococcus epidermidis facilitates generation of commensal-specific tolerance and CD4⁺ regulatory T cells (Tregs), we ask whether this response is perturbed by gut inflammation. Chemically induced colitis is accompanied by intestinal expansion of S. epidermidis and reduces gut-draining lymph node (dLN) commensal-specific Tregs. It also results in reduced commensal-specific Tregs in skin and skin-dLNs and increased skin neutrophils. Increased CD4⁺ circulation between gut and skin dLN suggests that the altered cutaneous response is initiated in the colon, and resistance to colitis-induced effects in Cd4^creIl1r1^fl/fl mice implicate interleukin (IL)-1 in mediating the altered commensal-specific response. These findings provide mechanistic insight into observed connections between inflammatory skin and intestinal diseases.