Training Researchers in the Field of Religion, Spirituality, and Health: Experiences from a Workshop in the United States and Recommendations for Future Workshop Curricula.

Although a substantial amount of research has been conducted in the field of religion, spirituality, and health, much still needs to be done. Training of researchers to conduct studies in the field of religion, spirituality, and health is essential for continued academic and methodological rigor. Such training should be globally oriented to ensure both representation and evidence from non-western cultures which is currently lacking. While little attention is given to this area in mainstream contemporary academic curricula, some researchers in the field have provided exceptional leadership in designing programs to train future researchers. In this commentary, the authors who participated in one such training program at Duke University, offer their insights based on a qualitative descriptive analysis of survey responses from a sample of participants. These insights relate to participants' perceptions of the most valuable experiences from a workshop on religion, spirituality, and health, and include recommendations for future content in training programs in this field. The multicultural aspect of the program with researchers, clinicians, and other professionals from 17 different countries was the most enriching aspect of the workshop. One of the key recommendations for future training efforts is to dedicate workshop time for participants to work collaboratively in the design and plan for international and interdisciplinary research projects with guidance from faculty.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [Tobias Anker] Last name [Stripp]. Also, kindly confirm the details in the metadata are correct.They are correct.

The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development.

Natural killer (NK) cells are a subset of lymphocytes crucial for innate immunity and modification of adaptive immune responses. In contrast to commitment to the T cell or B cell lineage, little is known about NK cell lineage commitment. Here we show that the basic leucine zipper (bZIP) transcription factor E4BP4 (also called NFIL3) is essential for generation of the NK cell lineage. E4BP4-deficient mice (Nfil3(-/-); called 'E4bp4(-/-)' here) had B cells, T cells and NKT cells but specifically lack NK cells and showed severely impaired NK cell-mediated cytotoxicity. Overexpression of E4bp4 was sufficient to increase NK cell production from hematopoietic progenitor cells. E4BP4 acted in a cell-intrinsic manner 'downstream' of the interleukin 15 receptor (IL-15R) and through the transcription factor Id2. E4bp4(-/-) mice may provide a model for definitive analysis of the contribution of NK cells to immune responses and pathologies.

Regulatory T cells--a journey from rodents to the clinic.

Over the past decade our understanding about a subset of T lymphocytes, now termed regulatory T cells (Tregs) and previously known as suppressor T cells, has increased immensely. Tregs can induce and maintain immune tolerance and have the capacity to facilitate antigen-specific long-term graft survival successfully in animals receiving allogeneic organ transplants. The development of approaches to generate alloantigen reactive Tregs would provide an exciting and effective adjunct or alternative therapy to the life-long program of immunosuppression currently necessary to prevent graft rejection in the clinical setting. This review will focus on how rodent experimental models have helped us to figure out how Tregs could be induced in humans and harnessed to enable long-term transplant acceptance.

Understanding FOXP3: progress towards achieving transplantation tolerance.

Regulatory T cells (Treg) suppress immune responses, making them an exciting therapeutic target for achieving operational transplant tolerance. Recent observations have identified forkhead box P3 (FOXP3) as a master gene required for the development and function of Treg. Improving our understanding of FOXP3 may facilitate methods for identifying and generating Treg.

Alpha-1,2-mannosidase and hence N-glycosylation are required for regulatory T cell migration and allograft tolerance in mice.

BACKGROUND: Specific immunological unresponsiveness to alloantigens can be induced in vivo by treating mice with a donor alloantigen in combination with a non-depleting anti-CD4 antibody. This tolerance induction protocol enriches for alloantigen reactive regulatory T cells (Treg). We previously demonstrated that alpha-1,2-mannosidase, an enzyme involved in the synthesis and processing of N-linked glycoproteins, is highly expressed in tolerant mice, in both graft infiltrating leukocytes and peripheral blood lymphocytes. PRINCIPAL FINDINGS: In this study we have identified that alpha-1,2-mannosidase expression increases in CD25(+)CD4(+) Treg when they encounter alloantigen in vivo. When alpha-1,2-mannosidase enzyme activity was blocked, Treg retained their capacity to suppress T cell proliferation in vitro but were unable to bind to physiologically relevant ligands in vitro. Further in vivo analysis demonstrated that blocking alpha-1,2-mannosidase in Treg resulted in the migration of significantly lower numbers to the peripheral lymph nodes in skin grafted mice following adoptive transfer, where they were less able to inhibit the proliferation of naïve T cells responding to donor alloantigen and hence unable prevent allograft rejection in vivo. SIGNIFICANCE: Taken together, our results suggest that activation of alloantigen reactive Treg results in increased alpha-1,2-mannosidase expression and altered N-glycosylation of cell surface proteins. In our experimental system, altered N-glycosylation is not essential for intrinsic Treg suppressive capacity, but is essential in vivo as it facilitates Treg migration to sites where they can regulate immune priming. Migration of Treg is central to their role in regulating in vivo immune responses and may require specific changes in N-glycosylation upon antigen encounter.

Regulatory T cells in transplantation: transferring mouse studies to the clinic.

Switching the balance from rejection of major histocompatibility-mismatched grafts toward long-term tolerance of donor grafts, with the need for minimal immunosuppressive drugs, is a major transplantation goal. Regulatory T cells (Treg) can induce and maintain antigen-specific immune tolerance and facilitate allogeneic graft survival successfully in animals. This review will focus on the valuable insights experimental mouse models have given us into the effects of currently used immunosuppressive reagents on Treg, the Treg transcription factor forkhead box P3, and strategies to expand or induce alloantigen-reactive Treg in vivo and in vitro. These have facilitated the translation of strategies for promoting transplantation tolerance towards a new clinical era.

Anti-CD4-mediated selection of Treg in vitro - in vitro suppression does not predict in vivo capacity to prevent graft rejection.

Regulatory T cells (Treg) have been shown to play a role in the prevention of autoimmune diseases and transplant rejection. Based on an established protocol known to generate alloantigen reactive Treg in vivo, we have developed a strategy for the in vitro selection of Treg. Stimulation of unfractionated CD4(+) T cells from naive CBA.Ca (H2(k)) mice with C57BL/10 (H2(b)) splenocytes in the presence of an anti-CD4 antibody, YTS 177, resulted in the selection of Treg able to inhibit proliferation of naive T cells. In vivo, the cells were able to prevent rejection of 80% C57BL/10 skin grafts when co-transferred to CBA.Rag(-/-) mice together with naive CD45RB(high)CD4(+) cells. Purification of CD62L(+)CD25(+)CD4(+) cells from the cultures enriched for cells with regulatory activity; as now 100% survival of C57BL/10 skin grafts was achieved. Furthermore, differentiation of Treg could be also achieved when using purified CD25(-)CD4(+) naive T cells as a starting population. Interestingly, further in vitro expansion resulted in a partial loss of CD4(+) cells expressing both CD62L and CD25 and abrogation of their regulatory activity in vivo. This study shows that alloantigen stimulation in the presence of anti-CD4 in vitro provides a simple and effective strategy to generate alloreactive Treg.