SummaryTissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8+ Trm cells on a compartmental and functional basis. In human skin epithelia, CD8+CD49a+ Trm cells produced interferon-γ, whereas CD8+CD49a− Trm cells produced interleukin-17 (IL-17). In addition, CD8+CD49a+ Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response. In skin from patients with vitiligo, where melanocytes are eradicated locally, CD8+CD49a+ Trm cells that constitutively expressed perforin and granzyme B accumulated both in the epidermis and dermis. Conversely, CD8+CD49a– Trm cells from psoriasis lesions predominantly generated IL-17 responses that promote local inflammation in this skin disease. Overall, CD49a expression delineates CD8+ Trm cell specialization in human epithelial barriers and correlates with the effector cell balance found in distinct inflammatory skin diseases.

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The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2+ and CRTH2− ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-δ rearrangement. Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.

Aim. To evaluate capsule endoscopy in terms of incomplete examinations and capsule retentions and to find risk factors for these events. Material and Methods. This retrospective and consecutive study includes data from 2300 capsule enteroscopy examinations, performed at four different hospitals in Stockholm, Sweden from 2003 to 2009. Results. The frequency of incomplete examinations was 20%. Older age, male gender, suspected, and known Crohn's disease were risk factors for an incomplete examination. The PillCam capsule had the highest rate of completed examinations. Capsule retention occurred in 1.3% (n = 31). Risk factors for capsule retention were known Crohn's disease and suspected tumor. Complications of capsule retention were acute obstructive symptoms in six patients and one death related to complications after acute surgical capsule retrieval. Conclusion: Capsule endoscopy is considered a safe procedure, although obstructive symptoms and serious complications due to capsule retention can be found in a large series of patients.

In light of the beneficial targeting of IL-23/12 in patients with IBD, 1,25D appears as an interesting therapeutic agent that inhibits the IL-23 receptor pathway, providing a novel mechanism for how ILC3s could be manipulated to regulate intestinal inflammation.

The Ikaros family of transcription factors (TFs) are important regulators of lymphocyte function. However, their roles in human innate lymphoid cell (ILC) function remain unclear. Here, we found that Ikaros (IKZF1) is expressed by all ILC subsets, including NK cells, in blood, tonsil, and gut, while Helios (IKZF2) is preferentially expressed by ILC3 in tonsil and gut. Aiolos (IKZF3) followed the expression pattern of T-bet and Eomes, being predominantly expressed by ILC1 and NK cells. Differentiation of IFN-γ-producing ILC1 and NK cells from ILC3 by IL-1β plus IL-12-stimulation was associated with upregulation of T-bet and Aiolos. Selective degradation of Aiolos and Ikaros by lenalidomide suppressed ILC1 and NK cell differentiation and expression of ILC1 and NK cell-related transcripts (LEF1, PRF1, GRZB, CD244, NCR3, and IRF8). In line with reduced ILC1/NK cell differentiation, we observed an increase in the expression of the ILC3-related TF Helios, as well as ILC3 transcripts (TNFSF13B, IL22, NRP1, and RORC) and in the frequency of IL-22 producing ILC3 in cultures with IL-1β and IL-23. These data suggest that suppression of Aiolos and Ikaros expression inhibits ILC1 and NK cell differentiation while ILC3 function is maintained. Hence, our results open up for new possibilities in targeting Ikaros family TFs for modulation of type 1/3 immunity in inflammation and cancer.Keywords: Aiolos r Ikaros r ILC r lenalidomide r NK cells Additional supporting information may be found online in the Supporting Information section at the end of the article.

Inflammatory lesions in the small bowel diagnosed by CE in patients with suspected Crohn´s disease are correlated to fecal calprotectin and CRP, but not to symptoms.

The temporal and spatial expression of thirteen novel spermatid-specific genes corresponding to cDNA clones isolated from an adult mouse testis library was analyzed. Northern analysis of RNA from seminiferous tubules at defined stages of the rat and mouse seminiferous epithelial cycle and in situ hybridization of testis sections revealed that these mRNAs were expressed in a stage-specific manner. The expression of all mRNAs was first detected in early round spermatids, and it increased to abundance during stages VII-VIII of the epithelial cycle. Twelve out of thirteen mRNAs were found not only in round spermatids but also in transcriptionally inactive elongated spermatids, suggesting that they are stored and regulated at the translational level. The variation in the length of the poly(A) tail was detected for four of the transcripts, represented by cDNA clones MTEST70, MTEST627, MTEST641, and MTEST643 at defined stages of the cycle. Similarity in the stage-specific expression pattern displayed by this group of haploid-specific genes strongly suggests the presence of common regulatory mechanisms that act during spermiogenesis, and these genes also provide a means for further studies of these mechanisms.