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Sa1786 Paradoxically Increased FOXP3+ Regulatory T Cells in Ulcerative Colitis Are Not Activated CD4+ Effector T Cells
modulation where helminth-mediated decrease in IRAK-1 gene expression in intestinal CD4 T cells is associated with a selective expansion of FoxP3 positive CD4 T lymphocytes and decrease in IL-17 production.
Sa1788 Ileocolic Resection Recruits CD11c+Cd103+ Dendritic Cells to the Gut and Prevents the Release of Pro-Inflammatory Cytokines in a Surgical Mouse Model Troy Perry, Richard N. Fedorak, Bryan Dicken, Karen Madsen
AGA Abstracts
Sa1786
Background: Ileocolic resection (ICR) is the most common surgical procedure performed for Crohn's disease, with recurrences commonly occurring early at the site of anastomosis. Immunologic factors leading to recurrence have yet to be defined. Dendritic cells (DC) are central to immune responses in the gut. In particular, the CD11c+CD103+ subset is known to traffic luminal antigens from the lamina propria to mesenteric lymph nodes where they induce T regulatory cells. Gut DCs may be further subdivided based on the expression of markers CD11b and CX3CR1. Aims: This study was designed to evaluate changes in gut DC populations resulting from ICR, and correlate these changes with the intestinal response to a gut insult after surgery. Methods: ICR with anastomosis was performed in adult 129S1/ SvlmJ wild type mice. Results were compared to mice receiving sham surgery or no surgery. After 9 (short-term) or 23 (long-term) days following ICR, mice were given dextran sodium sulfate (DSS :2.5%) for 5 days followed by sacrifice. Fecal occult blood measurements were taken daily. Myeloperoxidase (MPO), IL-1β, KC/GRO, TNF-α, TGF-β, IL-12, IFN-γ, IL-6, IL-10, IL-17 and IL-23 levels were determined in the terminal ileum (TI), and colon. TI Bacteria load was measured using qPCR. Histologic inflammatory scoring, and double immunofluorescence for CD11c with CD103, or CD11b, or CX3CR1 was performed. Results: ICR caused an initial elevation of MPO, KC/GRO, and IL-1 β (p,0.05) in the TI and colon, but these decreased in the TI of long-term mice; conversely, bacteria increased in this tissue. Immunoflourescence revealed CD11c+CD11b+CD103- DCs as the predominate subtype in controls. After ICR, CD11c+CD103+ DCs became the dominant subtype (p ,0.001). This effect diminished in the TI of long-term mice, but remained in the colon. DSS induced occult blood positive stools 48 hours earlier in ICR groups vs. controls, and this was associated with immunosuppression, and lack of cytokine response. In contrast, control mice had significant elevations in colonic MPO, IL-1 β, KC/GRO, TNF-α, IFN-γ, IL-6, IL10, IL-17 and IL-23 (p,0.05). TI CD11c+CD103+ DCs decreased in short-term ICR mice after DSS, but increased in long-term mice following DSS. Colonic CD11c+CD103+ DCs remained elevated across all ICR groups. Conclusions: ICR causes an initial innate inflammatory response as evidenced by elevated MPO, KC/GRO, and IL-1 β. The increased numbers of CD11c+CD103+ DCs at the surgical site coupled with a blunted cytokine response suggests a possible induction of tolerance, which may help explain the increased numbers of bacteria at the TI in the long-term mice. This study reveals a potential mechanism whereby increased tolerance to gut microbes after surgery may allow enhanced bacterial loads to occur at surgical sites contributing to Crohn's disease relapse after ICR.
Paradoxically Increased FOXP3+ Regulatory T Cells in Ulcerative Colitis Are Not Activated CD4+ Effector T Cells James D. Lord, Anna Sherwood, Janice Chen, Richard C. Thirlby, Christopher Carlson Background: CD4+ "Natural" regulatory T cells (nTregs) constitutively express the nuclear transcription factors FOXP3 and Helios, and play a central role in down-regulating inflammation. However, pro-inflammatory FOXP3- CD4+ effector T cells can transiently express FOXP3 upon activation to become Helios-negative "induced" Tregs (iTregs), with a less clear role in immunoregulation. Such activation-induced FOXP3 expression has been hypothesized to account for a paradoxically increased FOXP3+ fraction of CD4+ lamina propria lymphocytes (LPL) observed in the inflamed colons of patients with ulcerative colitis (UC). Methods: To determine if FOXP3+ LPL in UC are the activated clones of otherwise FOXP3effector cells, we employed a novel technology to sequence the clonally unique T cell receptor (TCR) V beta hypervariable region of CD4+ T cell populations sorted from the surgically resected inflamed versus uninflamed colonic LPL or the mesenteric lymph nodes (MLN) of three patients with ulcerative colitis (UC), or the colonic LPL of three patients without IBD. From each specimen, FOXP3+ Tregs were sorted into fractions with and without the putative nTreg marker Helios, while FOXP3-, CD45RA- cells were sorted into CD161+ (including pro-inflammatory "Th17" cells), CD161- (excluding Th17's), and CD38+ (activated) cells. Results: The clonal diversity of Tregs was greater in MLN than LPL, but it was no different between LPL from patients with or without UC. Although more FOXP3+ cells were seen in inflamed versus uninflamed colon, this expansion was seen in both Helios+ and Helioscells. 5-35% of FOXP3+ LPL shared TCR sequences between Helios+ and Helios- fractions, revealing considerable plasticity between these populations, but this repertoire overlap was no different between patients with versus without UC. Even less overlap was seen between FOXP3- effector T cells and FOXP3+, Helios+ "nTregs" in the colon, again regardless of UC and inflammation. A somewhat larger overlap was seen between FOXP3- cells and the Helios- "iTreg" fraction, particularly in UC, but this overlap was heterogeneous between patients, and again was no larger than the overlap between Helios+ and Helios- Tregs. Much less overlap was seen in MLN, where Helios+ FOXP3+ nTregs shared almost no TCR repertoire with other populations. Conclusions: Through TCR sequencing, we demonstrated that only a minority of FOXP3+, and particularly Helios+, Tregs share a TCR sequence, and hence clonal origin, with FOXP3- effector populations. This refutes the hypothesis that the copious FOXP3+ LPL in UC are an activated fraction of otherwise FOXP3- effector T cells. Furthermore, the finding that Helios- FOXP3+ LPL have more in common with Helios+ than FOXP3- LPL suggest that they are more commonly derived from Helios+ nTreg precursors than activated effector T cells.
Sa1789 Bone Marrow Dendritic Cells Exposed to Trans-Fatty Acids Exacerbate DSSInduced Colitis Through Promotion of TH17 Differentiation and UpRegulation of Proinflammatory Cytokines Yoshikiyo Okada, Yoshikazu Tsuzuki, Hirokazu Sato, Kazuyuki Narimatsu, Ryota Hokari, Kengo Tomita, Chie Kurihara, Shunsuke Komoto, Chikako Watanabe, Atsushi Kawaguchi, Shigeaki Nagao, Soichiro Miura
Sa1787 Kruppel Like Factor-10 Regulates Adaptive FOXP3+ Treg Cell Development in a TGFβ Dependent Manner Sahil Khanna, Phyllis A. Svingen, Maneesh Dave, Yuning Xiong, Olga F. Sarmento, Thomas C. Smyrk, William A. Faubion
BACKGROUND Fatty acids in our daily diet are broadly classified into cis and trans fatty acids (TFAs). Although several cis-form of fatty acids are reported to differentially modulate the maturation of dendritic cells (DCs), little is known regarding the direct effects of transform fatty acids (TFAs) on DCs immune functions and intestinal inflammation. In this study, we examined the effects of TFAs on the bone marrow DCs (BMDCs) cell surface molecules and cytokine profiles and whether adoptive transfer of DCs treated by TFAs affect DSSinduced colonic inflammation. MATELIALS AND METHODS BMDCs were generated from the bone marrow of C57BL/6 mice by culture in GM-CSF. BMDCs were incubated with elaidic acid (TFA) or oleic acid (cis-form) was added for 24 hours. After incubation cells (FAstreated BMDCs) were harvested, and mRNA levels of cytokines and cell surface molecules were determined. In another sets of in vivo experiments, C57BL6 mice were given 2.5% of DSS treatment in drinking water for seven days. On the day 3 and day 6, FAs-treated BMDCs were transferred by a single intraperitoneal administration. The degree of colonic inflammation was evaluated. mRNA levels of cytokines in colonic tissue and MLN were also determined. RESULTS TFA exposure in vitro significantly increased the expression of B7-1 and MHC Class II in BMDCs compared with cis-form treatment. mRNA levels of IL-1 β, IL-12p40 and IL-23p19 in BMDCs were significantly up-regulated by TFA treatment than in the case of cis-form treatment. In vivo study, a significant aggravation of colonic shortening was observed in the DSS with TFA-treated BMDCs compared to the DSS with cis-treated group. The incidence of rectal bleeding and diarrhea on the day 6 to 7 was increased by the transfer of TFA-treated BMDCs compared with the case of cis-form treatment. Moreover, mRNA levels of IL-1β, TNF-α and IL-17A in the colonic tissue were also significantly increased by the transfer of TFA-treated BMDCs. mRNA levels of ROR- γt in MLN were significantly elevated by the transfer of TFA-treated BMDCs compared with the case of cis-form treatment. CONCLUSIONS TFAs induce a phenotypic change in BMDCs characterized by increased proinflammatory cytokines and cell surface molecules in vitro. In DSS-induced colitis with TFA-treated BMDCs transfer, those colonic inflammation significantly exacerbates accompanied by colonic shortening and up-regulation of proinflamatory cytokines in colonic mucosa. In addition, mRNA levels of ROR-γt in MLN, a master regulator guiding Th17 cell differentiation, were enhanced in TFA-treated BMDCs transfer. Our data suggest that TFAs may exacerbate colonic inflammation such as in inflammatory bowel disease and have the ability to promote Th17 differentiation in bone-marrow derived DCs.
Background: Adaptive FOXP3+ Treg cells develop outside the thymus, in response to TGF β and antigen, and are critically important in intestinal immunologic homeostasis. Kruppellike factors (KLFs) constitute a family of diverse transcription regulatory proteins that are important transcriptional modifiers of T lymphocyte biology. Dysregulation of FOXP3, a key driver of the T cell regulatory program leads to intestinal inflammation in both mice and humans. We have previously demonstrated that the absence of KLF10 silences FOXP3 and causes enhanced colitis in KLF10 -/- mice. Aims: To study the role of KLF10 and TGF β in the regulation of adaptive FOXP3+ Treg cell development Methods: KLF10-/- and age & sex-matched C57BL/6 wild type mice were used for isolation of CD4+ Tcells, Naïve CD4+CD62L+ Tcells, and Treg cells as needed in various experiments. Both KLF10-/- and C57BL/6 mice were crossed to TGF β +/+ mice to evaluate the role of TGF β in regulation of adaptive FOXP3+ Treg cell development by KLF10. RAG1 -/- mice were used for adoptive transfer of T-cells for expansion and generation of bone marrow chimeras (KLF10 -/- or C57BL/6) for dextran sodium sulfate (DSS) induced colitis. Results: Immuno-characterization of KLF10-/- and C57BL/6 mice demonstrated a deficit of FOXP3 positive Treg cells in the spleens and mesenteric lymph nodes of KLF10-/- mice. Futhermore, analysis of KLF10-/x TGFβ and C57BL/6 x TGFβ mice demonstrated that the presence of TGF β enhanced the production of FOXP3 Treg cells in splenocytes in both C57BL/6 and KLF10-/- mice, but higher in C57BL/6 mice. Adoptive transfer of Treg depleted CD4+/+ splenocytes from KLF10 -/- or C57BL/6 mice into RAG1 -/- mice demonstrated a 2-3 fold higher upregulation of FOXP3 positive cells in the peripheral blood and spleens of RAG1 -/- mice injected with Treg depleted CD4+/+ cells from C57BL/6 mice, suggesting a deficit in adaptive Treg generation in KLF10-/- mice. In vitro suppression assays comparing splenic KLF10-/- Treg cells to C57BL/6 Treg cells, assessing the ability to suppress antigen driven CD4+/+ Tcell proliferation, both KLF10-/- Treg cells to C57BL/6 Treg cells demonstrated the ability to suppress CD4+/+ Tcell proliferation from responder cells from both KLF10-/- and C57BL6 mice; suggesting that there are functional natural Treg cells present in KLF10-/- mice; and the deficit is limited to adaptive Treg cell generation. DSS colitis models of bone marrow chimeras in RAG1 -/- mice demonstrated heightened colitis in the KLF10-/- mice compared to C57BL/6 mice suggesting the adaptive Treg cell development is affected at the bone marrow level. Conclusions: KLF10-/- mice lack an adaptive Treg cell compartment, which makes the mice have a heightened susceptibility to experimental colitis. Natural Tregs are functionally preserved in this mouse.
AGA Abstracts
S-306
Sa1788 Ileocolic Resection Recruits CD11c+Cd103+ Dendritic Cells to the Gut and Prevents the Release of Pro-Inflammatory Cytokines in a Surgical Mouse Model Troy Perry, Richard N. Fedorak, Bryan Dicken, Karen Madsen
AGA Abstracts
Sa1786
Background: Ileocolic resection (ICR) is the most common surgical procedure performed for Crohn's disease, with recurrences commonly occurring early at the site of anastomosis. Immunologic factors leading to recurrence have yet to be defined. Dendritic cells (DC) are central to immune responses in the gut. In particular, the CD11c+CD103+ subset is known to traffic luminal antigens from the lamina propria to mesenteric lymph nodes where they induce T regulatory cells. Gut DCs may be further subdivided based on the expression of markers CD11b and CX3CR1. Aims: This study was designed to evaluate changes in gut DC populations resulting from ICR, and correlate these changes with the intestinal response to a gut insult after surgery. Methods: ICR with anastomosis was performed in adult 129S1/ SvlmJ wild type mice. Results were compared to mice receiving sham surgery or no surgery. After 9 (short-term) or 23 (long-term) days following ICR, mice were given dextran sodium sulfate (DSS :2.5%) for 5 days followed by sacrifice. Fecal occult blood measurements were taken daily. Myeloperoxidase (MPO), IL-1β, KC/GRO, TNF-α, TGF-β, IL-12, IFN-γ, IL-6, IL-10, IL-17 and IL-23 levels were determined in the terminal ileum (TI), and colon. TI Bacteria load was measured using qPCR. Histologic inflammatory scoring, and double immunofluorescence for CD11c with CD103, or CD11b, or CX3CR1 was performed. Results: ICR caused an initial elevation of MPO, KC/GRO, and IL-1 β (p,0.05) in the TI and colon, but these decreased in the TI of long-term mice; conversely, bacteria increased in this tissue. Immunoflourescence revealed CD11c+CD11b+CD103- DCs as the predominate subtype in controls. After ICR, CD11c+CD103+ DCs became the dominant subtype (p ,0.001). This effect diminished in the TI of long-term mice, but remained in the colon. DSS induced occult blood positive stools 48 hours earlier in ICR groups vs. controls, and this was associated with immunosuppression, and lack of cytokine response. In contrast, control mice had significant elevations in colonic MPO, IL-1 β, KC/GRO, TNF-α, IFN-γ, IL-6, IL10, IL-17 and IL-23 (p,0.05). TI CD11c+CD103+ DCs decreased in short-term ICR mice after DSS, but increased in long-term mice following DSS. Colonic CD11c+CD103+ DCs remained elevated across all ICR groups. Conclusions: ICR causes an initial innate inflammatory response as evidenced by elevated MPO, KC/GRO, and IL-1 β. The increased numbers of CD11c+CD103+ DCs at the surgical site coupled with a blunted cytokine response suggests a possible induction of tolerance, which may help explain the increased numbers of bacteria at the TI in the long-term mice. This study reveals a potential mechanism whereby increased tolerance to gut microbes after surgery may allow enhanced bacterial loads to occur at surgical sites contributing to Crohn's disease relapse after ICR.
Paradoxically Increased FOXP3+ Regulatory T Cells in Ulcerative Colitis Are Not Activated CD4+ Effector T Cells James D. Lord, Anna Sherwood, Janice Chen, Richard C. Thirlby, Christopher Carlson Background: CD4+ "Natural" regulatory T cells (nTregs) constitutively express the nuclear transcription factors FOXP3 and Helios, and play a central role in down-regulating inflammation. However, pro-inflammatory FOXP3- CD4+ effector T cells can transiently express FOXP3 upon activation to become Helios-negative "induced" Tregs (iTregs), with a less clear role in immunoregulation. Such activation-induced FOXP3 expression has been hypothesized to account for a paradoxically increased FOXP3+ fraction of CD4+ lamina propria lymphocytes (LPL) observed in the inflamed colons of patients with ulcerative colitis (UC). Methods: To determine if FOXP3+ LPL in UC are the activated clones of otherwise FOXP3effector cells, we employed a novel technology to sequence the clonally unique T cell receptor (TCR) V beta hypervariable region of CD4+ T cell populations sorted from the surgically resected inflamed versus uninflamed colonic LPL or the mesenteric lymph nodes (MLN) of three patients with ulcerative colitis (UC), or the colonic LPL of three patients without IBD. From each specimen, FOXP3+ Tregs were sorted into fractions with and without the putative nTreg marker Helios, while FOXP3-, CD45RA- cells were sorted into CD161+ (including pro-inflammatory "Th17" cells), CD161- (excluding Th17's), and CD38+ (activated) cells. Results: The clonal diversity of Tregs was greater in MLN than LPL, but it was no different between LPL from patients with or without UC. Although more FOXP3+ cells were seen in inflamed versus uninflamed colon, this expansion was seen in both Helios+ and Helioscells. 5-35% of FOXP3+ LPL shared TCR sequences between Helios+ and Helios- fractions, revealing considerable plasticity between these populations, but this repertoire overlap was no different between patients with versus without UC. Even less overlap was seen between FOXP3- effector T cells and FOXP3+, Helios+ "nTregs" in the colon, again regardless of UC and inflammation. A somewhat larger overlap was seen between FOXP3- cells and the Helios- "iTreg" fraction, particularly in UC, but this overlap was heterogeneous between patients, and again was no larger than the overlap between Helios+ and Helios- Tregs. Much less overlap was seen in MLN, where Helios+ FOXP3+ nTregs shared almost no TCR repertoire with other populations. Conclusions: Through TCR sequencing, we demonstrated that only a minority of FOXP3+, and particularly Helios+, Tregs share a TCR sequence, and hence clonal origin, with FOXP3- effector populations. This refutes the hypothesis that the copious FOXP3+ LPL in UC are an activated fraction of otherwise FOXP3- effector T cells. Furthermore, the finding that Helios- FOXP3+ LPL have more in common with Helios+ than FOXP3- LPL suggest that they are more commonly derived from Helios+ nTreg precursors than activated effector T cells.
Sa1789 Bone Marrow Dendritic Cells Exposed to Trans-Fatty Acids Exacerbate DSSInduced Colitis Through Promotion of TH17 Differentiation and UpRegulation of Proinflammatory Cytokines Yoshikiyo Okada, Yoshikazu Tsuzuki, Hirokazu Sato, Kazuyuki Narimatsu, Ryota Hokari, Kengo Tomita, Chie Kurihara, Shunsuke Komoto, Chikako Watanabe, Atsushi Kawaguchi, Shigeaki Nagao, Soichiro Miura
Sa1787 Kruppel Like Factor-10 Regulates Adaptive FOXP3+ Treg Cell Development in a TGFβ Dependent Manner Sahil Khanna, Phyllis A. Svingen, Maneesh Dave, Yuning Xiong, Olga F. Sarmento, Thomas C. Smyrk, William A. Faubion
BACKGROUND Fatty acids in our daily diet are broadly classified into cis and trans fatty acids (TFAs). Although several cis-form of fatty acids are reported to differentially modulate the maturation of dendritic cells (DCs), little is known regarding the direct effects of transform fatty acids (TFAs) on DCs immune functions and intestinal inflammation. In this study, we examined the effects of TFAs on the bone marrow DCs (BMDCs) cell surface molecules and cytokine profiles and whether adoptive transfer of DCs treated by TFAs affect DSSinduced colonic inflammation. MATELIALS AND METHODS BMDCs were generated from the bone marrow of C57BL/6 mice by culture in GM-CSF. BMDCs were incubated with elaidic acid (TFA) or oleic acid (cis-form) was added for 24 hours. After incubation cells (FAstreated BMDCs) were harvested, and mRNA levels of cytokines and cell surface molecules were determined. In another sets of in vivo experiments, C57BL6 mice were given 2.5% of DSS treatment in drinking water for seven days. On the day 3 and day 6, FAs-treated BMDCs were transferred by a single intraperitoneal administration. The degree of colonic inflammation was evaluated. mRNA levels of cytokines in colonic tissue and MLN were also determined. RESULTS TFA exposure in vitro significantly increased the expression of B7-1 and MHC Class II in BMDCs compared with cis-form treatment. mRNA levels of IL-1 β, IL-12p40 and IL-23p19 in BMDCs were significantly up-regulated by TFA treatment than in the case of cis-form treatment. In vivo study, a significant aggravation of colonic shortening was observed in the DSS with TFA-treated BMDCs compared to the DSS with cis-treated group. The incidence of rectal bleeding and diarrhea on the day 6 to 7 was increased by the transfer of TFA-treated BMDCs compared with the case of cis-form treatment. Moreover, mRNA levels of IL-1β, TNF-α and IL-17A in the colonic tissue were also significantly increased by the transfer of TFA-treated BMDCs. mRNA levels of ROR- γt in MLN were significantly elevated by the transfer of TFA-treated BMDCs compared with the case of cis-form treatment. CONCLUSIONS TFAs induce a phenotypic change in BMDCs characterized by increased proinflammatory cytokines and cell surface molecules in vitro. In DSS-induced colitis with TFA-treated BMDCs transfer, those colonic inflammation significantly exacerbates accompanied by colonic shortening and up-regulation of proinflamatory cytokines in colonic mucosa. In addition, mRNA levels of ROR-γt in MLN, a master regulator guiding Th17 cell differentiation, were enhanced in TFA-treated BMDCs transfer. Our data suggest that TFAs may exacerbate colonic inflammation such as in inflammatory bowel disease and have the ability to promote Th17 differentiation in bone-marrow derived DCs.
Background: Adaptive FOXP3+ Treg cells develop outside the thymus, in response to TGF β and antigen, and are critically important in intestinal immunologic homeostasis. Kruppellike factors (KLFs) constitute a family of diverse transcription regulatory proteins that are important transcriptional modifiers of T lymphocyte biology. Dysregulation of FOXP3, a key driver of the T cell regulatory program leads to intestinal inflammation in both mice and humans. We have previously demonstrated that the absence of KLF10 silences FOXP3 and causes enhanced colitis in KLF10 -/- mice. Aims: To study the role of KLF10 and TGF β in the regulation of adaptive FOXP3+ Treg cell development Methods: KLF10-/- and age & sex-matched C57BL/6 wild type mice were used for isolation of CD4+ Tcells, Naïve CD4+CD62L+ Tcells, and Treg cells as needed in various experiments. Both KLF10-/- and C57BL/6 mice were crossed to TGF β +/+ mice to evaluate the role of TGF β in regulation of adaptive FOXP3+ Treg cell development by KLF10. RAG1 -/- mice were used for adoptive transfer of T-cells for expansion and generation of bone marrow chimeras (KLF10 -/- or C57BL/6) for dextran sodium sulfate (DSS) induced colitis. Results: Immuno-characterization of KLF10-/- and C57BL/6 mice demonstrated a deficit of FOXP3 positive Treg cells in the spleens and mesenteric lymph nodes of KLF10-/- mice. Futhermore, analysis of KLF10-/x TGFβ and C57BL/6 x TGFβ mice demonstrated that the presence of TGF β enhanced the production of FOXP3 Treg cells in splenocytes in both C57BL/6 and KLF10-/- mice, but higher in C57BL/6 mice. Adoptive transfer of Treg depleted CD4+/+ splenocytes from KLF10 -/- or C57BL/6 mice into RAG1 -/- mice demonstrated a 2-3 fold higher upregulation of FOXP3 positive cells in the peripheral blood and spleens of RAG1 -/- mice injected with Treg depleted CD4+/+ cells from C57BL/6 mice, suggesting a deficit in adaptive Treg generation in KLF10-/- mice. In vitro suppression assays comparing splenic KLF10-/- Treg cells to C57BL/6 Treg cells, assessing the ability to suppress antigen driven CD4+/+ Tcell proliferation, both KLF10-/- Treg cells to C57BL/6 Treg cells demonstrated the ability to suppress CD4+/+ Tcell proliferation from responder cells from both KLF10-/- and C57BL6 mice; suggesting that there are functional natural Treg cells present in KLF10-/- mice; and the deficit is limited to adaptive Treg cell generation. DSS colitis models of bone marrow chimeras in RAG1 -/- mice demonstrated heightened colitis in the KLF10-/- mice compared to C57BL/6 mice suggesting the adaptive Treg cell development is affected at the bone marrow level. Conclusions: KLF10-/- mice lack an adaptive Treg cell compartment, which makes the mice have a heightened susceptibility to experimental colitis. Natural Tregs are functionally preserved in this mouse.
AGA Abstracts
S-306