How early-life colonization and subsequent exposure to the microbiota affect long-term tissue immunity remains poorly understood. Here, we show that the development of mucosal-associated invariant T (MAIT) cells relies on a specific temporal window, after which MAIT cell development is permanently impaired. This imprinting depends on early-life exposure to defined microbes that synthesize riboflavin-derived antigens. In adults, cutaneous MAIT cells are a dominant population of interleukin-17A (IL-17A)–producing lymphocytes, which display a distinct transcriptional signature and can subsequently respond to skin commensals in an IL-1–, IL-18–, and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells, which sequentially controls both tissue-imprinting and subsequent responses to injury.
Our results indicate distinct risks for HPV and LSIL. In addition, most women with HPV infection in our study did not develop LSIL within a median follow-up period of 60 months. These findings underscore the hypothesis that certain biological risks thought to be associated with LSIL are, in fact, risks for acquisition of HPV. Cigarette smoking was a risk specific to LSIL, supporting the role of tobacco in neoplastic development.
Highlights d 3D imaging defines ILC2 niches in perivascular regions of multiple tissues d ILC2s localize with fibroblast-like adventitial stromal cells (ASCs) d Lung ASCs produce IL-33 and TSLP to support ILC2 and Th2s d ILC2s promote ASC expansion and IL-33 production after helminth infection
Objective
To describe the natural history of CIN-2 in a prospective study of young women and to examine the behavioral and biologic factors associated with regression and progression.
Methods
Women aged 13 to 24 years referred for abnormal cytology and were found to have CIN-2 on histology were followed at 4-month intervals. Risks for regression defined as 3 consecutive negative cytology and histology visits and progression to CIN-3 were estimated using Cox proportional hazards regression models.
Findings
Ninety-five women with a mean age of 20.4 years (± 2.3) were entered into the analysis. Thirty-eight percent cleared by year 1, 63% by year 2 and 68% by year 3. Multivariable analysis found that recent N. gonorrhoeae infection (H.R. = 25.27 [95% C.I. 3.11, 205.42]) and medroxyprogesterone acetate use (per month) (H.R. = 1.02 [95% C.I. 1.003, 1.04]) were associated with regression. Factors associated with non-regression included combined hormonal contraception use (per month) (H.R. = 0.85 [95% C.I. 0.75, 0.97]) and persistence of HPV of any type (H.R. = 0.40 [95% C.I. 0.22, 0.72]). Fifteen percent of women showed progression by year 3. HPV 16/18 persistence (H.R. = 25.27 [95% C.I.2.65, 241.2, p = 0.005]) and HPV 16/18 status at last visit (H.R. = 7.25 [95% C.I. 1.07, 49.36); p < 0.05]) was associated with progression Because of the small sample size, other co-variates were not examined.
Conclusion
The high regression rate of CIN-2 supports clinical observation of this lesion in young women.
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